Close Concerns’ Reflections 2025 + 2026  – December 24, 2025

Diabetes Technology

Key Questions for 2026

Continuous Glucose Monitoring

1. What further clinical or real-world evidence is expected next from Abbott and how might upcoming data help define use cases for DGK and CKM?
2. How will manufacturers differentiate in an increasingly competitive CGM landscape, as longer-wear sensors and novel form factors expand user choice?
3. As CGM is increasing used earlier and earlier in disease progression, will there be formal guidance on using CGM as a diagnostic or risk-stratification tool for prediabetes and early-stage T1D?
4. How do uptake trends look after a full year of OTC CGM release for Dexcom’s Stelo and Abbott’s Lingo?
5. What other analytes are under consideration for analysis in multi-analyte sensors?
6. On CKM and the anticipated DGK sensor from Abbott, what is the current baseline understanding of ketone physiology among people with diabetes and providers, particularly around what constitutes as “normal” or “elevated” ketone levels in daily management?

Insulin Delivery

1. With three AID systems now formally indicated for T2D in the US (Tandem’s Control-IQ+, Medtronic’s MiniMed 780G, Insulet’s Omnipod 5) and CE-Mark expansion underway in Europe, how quickly will AID adoption accelerate in T2D now?
2. As AID systems expand beyond T1D, which additional safety components will be prioritized for adoption?
3. How will reimbursement frameworks evolve as AID systems move toward broader populations?
4. What policies will be required to ensure equitable access to AID systems for individuals facing socioeconomic barriers across different health systems?

Digital Health

1. What evidence will payers require to reimburse CGM-enabled digital health programs for people without insulin-treated diabetes or without diabetes?
2. With Omada Health expanding into GLP-1 RA prescribing and Signos targeting lifestyle-driven alternatives, how will these digital platforms complement provider guidance to support individuals?
3. How will the incorporation of AI-generated insights into digital health platforms reshape regulatory pathways and guidance in 2026?

What’s Coming in 2026?

Glucose Monitoring

Abbott

1. Expected regulatory application for approval of dual glucose-ketone (DGK) sensor.
2. Timeline of integrations of key insulin pump manufacturers with the anticipated DGK sensor.
3. Potential impact of CMS policy change on uptake.
4. Clinical impact of Libre-Epic integration.
5. Expanded commercial launch of Lingo in countries outside of the UK and the US.
6. Further incorporation of AI tools to help users understand their data.

Dexcom

7. Timeline and details on Dexcom G8 development at undisclosed investor event.
8. Real-world traction of Smart Basal and software updates.
9. Impact of G7 15 Day on material growth.
10. Discontinuation of the G6 and transition to G7 support.
11. Continued interoperability with several AID systems.

Medtronic

12. US impact post-Simplera Sync and Instinct launch.
13. Completion of MiniMed spinout.

Roche

14. Acceleration of Accu-Chek SmartGuide manufacturing and broader European rollout.
15. Expansion of Roche’s Kidney Klinrisk Algorithm.

Senseonics

16. Full in-house commercialization of Eversense in the US beginning at the start of 2026.
17. European launch of Eversense 365 following CE-Mark approval.
18. Regulatory and clinical progression of next-generation implantable CGMs: Gemini system and Freedom.

Insulin Delivery

Abbott

1. DGK integration with multiple pump partners.

Beta Bionics

2. Continued acceleration of iLet adoption, led by pharmacy-channel expansion.
3. Initiation and early readouts from clinical development of the bihormonal iLet system, following the start of human feasibility studies in late 2025.
4. Ongoing progress toward the Mint patch program targeting a 2027 commercial launch.

Diabeloop

5. European commercial launch of DBLG2 algorithm with ViCentra’s Kaleido patch pump, following CE-Mark approval.
6. Potential US commercial launch of DBLG2 algorithm following FDA clearance, though potential pump partners remain unclear.

Insulet

7. Omnipod 5 integration with Abbott’s FreeStyle Libre 3 Plus.
8. Evidence from STRIVE RCT and EVOLUTION 2 T2D feasibility study.

Medtronic

9. Expanded real-world adoption of MiniMed 780G across new indications.
10. Continued advancement of next-generation pump hardware: MiniMed Flex and MiniMed Fit FDA submission timelines.
11. Launch of Vivera fully closed loop US pivotal trial.
12. CE-Mark submission of MiniMed Flex.
13. FDA submission of MiniMed Fit.
14. Update on FDA application for MiniMed Go.

Roche

15. Accu-Chek SmartGuide CGM integration with mySugr app rollout in Europe.

Tandem

16. International launch of Mobi OUS.
17. Mobi Tubeless final stage testing.
18. Launch of pivotal study for Tandem’s fully-closed loop algorithm.
19. Tandem Source international expansion.
20. Mobi Android FDA clearance.
21. Continued broader global rollout of t:slim X2 integration with FreeStyle Libre 3 Plus.

Senseonics

22. Eversense 365 integration with Sequel’s twiist.

Sequel

23. Continued rollout of twiist throughout territories in the US.
24. FDA of twiist for T2D.

Tidepool

25. Continued integration of FreeStyle Libre with Tidepool.
26. Real-world dataset with Ōura Ring.

Ypsomed

27. Launch of new autoinjector line in Solothurn, Switzerland.

Digital Health

endo.digital

1. Continued rollout of DreaMed Advisor Pro 2.0 platform for people with T1D and T2D on MDI.

Glytec

2. Increasing rollout of Glytec in Ardent Health clinics and hospitals.
3. Updates on a US launch of the cobas pulse BGM.

mySugr (Roche)

5. Continued growth of mySugr beyond six million users.
6. Additional data readouts at conferences.

Omada Health

7. Continued integration of digital care and pharmacotherapy as GLP-1 prescribing integrated.

Teladoc

12. Further international growth with greater expansion into non-English speaking countries.
13. Increasing number of members enrolled in multiple chronic care programs.

Welldoc

15. Further expansion of BlueStar digital health platform to the EU. 

Themes

1. CGM reaches ~11 million global users at end of 3Q25, powered by adoption in growing populations; regulatory clearances expand competitive landscape

The CGM landscape continued its upward trajectory in 2025, driven by sustained uptake by people with T1D, rapid growth among those with T2D, and the continued emergence of real-world evidence supporting the multidimensional benefits of CGM use. Reflecting on the global market, we now estimate that approximately 11 million people were using CGM by the end of 3Q25, representing a 10% increase from the roughly 10 million users in late 2024 and a 38% increase from the eight million users in late 2023. See the figure below for an expanded time series on the estimated global CGM userbase over the last 15 years. The total CGM market reached ~$3.5 billion at the end of 3Q25, fueled by expanding international reimbursement for insulin-using T2D and national reimbursement for non-insulin T2D, and the first full year of over-the-counter (OTC) CGM availability in the US (Dexcom’s Stelo and Abbott’s Lingo). With nearly one million new users added globally, CGM continues to become entrenched as a foundational tool for glycemic monitoring and as a standard of care.

Estimated CGM Global Userbase (2010-3Q25)

Source: Close Concerns Knowledgebase

• Regulatory momentum was strong in 2025, with several clearances and launches shaping the competitive landscape, including: (i) FDA clearance of Dexcom’s G7 15 Day CGM for adults with diabetes in April; (ii) FDA clearance of Medtronic’s Simplera Sync in April; (iii) FDA De Novo authorization for the Biolinq Shine patch-based CGM in September; and (iv) Medtronic’s rollout of the Abbott-developed Instinct CGM beginning in September. Taken together, these clearances reflect a growing competitive landscape featuring new form-factor designs, ultimately bringing greater choice to people with diabetes.
  • Dexcom received FDA clearance for the G7 15 Day sensor in April for adults with T1D, T2D, and gestational diabetes, extending wear to 15.5 days (which includes the 12-hour grace period) and aligning more closely with Abbott’s 15-day Libre Plus sensors. Pivotal data presented at ATTD showed an overall MARD of 8.0%, modestly improving on 10-day G7 performance and meeting iCGM standards. The 15-day sensor officially launched in the US on December 1, with international launches expected in 2026.
  • Medtronic made significant regulatory and commercial progress on two new sensors in the US in 2025. Shortly after Medtronic’s SmartGuard algorithm received FDA clearance as an iAGC controller in September and MiniMed 7880G was cleared as an ACE pump (enabling integration with external sensors), the company began its rollout of Instinct, a 15-day iCGM developed by Abbott for exclusive use with MiniMed systems. A full launch was initiated at the beginning of December. Simplera Sync, meanwhile, received FDA clearance in April and has since rolled out.
  • Biolinq’s Shine received FDA De Novo Classification in September as the first Glucose Range Monitoring System, targeting adults with T2D not on insulin. The intradermal patch combines glucose, activity, and sleep metrics, with a color-coded LED display providing Time in Range (TIR) feedback visually and detailed insights via the app.
• A growing body of evidence reinforced that CGM meaningfully improves outcomes extending well beyond glycemic metrics, including impacts on renal risk, hypoglycemia prevention, and meaningful behavioral change. At ADA, a large retrospective analysis of adults with insulin-treated diabetes and CKD (n=65,839) showed that CGM initiation was associated with less CKD progression (29% vs. 35%) and a 14% slower decline in eGFR over three years, alongside greater reductions in A1c levels. At EASD, Dr. Hans DeVries reviewed RCTs and real-world evidence showing that CGM significantly reduces recurrent and severe hypoglycemia, particularly among individuals with impaired awareness, and reduces the frequency of emergency room visits. Collectively, these studies strengthen the case for CGM as a multidimensional chronic-disease tool with clinical, behavioral, and cardiometabolic benefits.
  • Of course, additional data emerged on its ability to improve A1c and TIR outcomes through diet, activity, and medication habit modifications, helping solidify CGM as a routine tool for people with T2D. Findings from the UNITE study in adults with T2D on non-insulin therapy showed that Dexcom G7 initiation significantly improved TIR in both nutrition-focused and a self-directed arm, while also driving measurable behavioral change such as improved Healthy Eating Index sores and greater confidence in food decisions among participants receiving structured guidance. Regardless, education still helps – CGM-integrated DSMES showed larger glycemic improvements for people with T2D on basal-only insulin. The ROUTE-T1D trial similarly demonstrated that a brief educator-led telehealth intervention improved A1c by 0.7% (from 10.7% to 10.0%) and increased CGM wear-time among socioeconomically diverse youth with historically low technology engagement. At ATTD, Drs. Hirsch, Beck, and Bergenstal also highlighted enhanced outcomes when CGM is paired with GLP-1 RA therapy, and Dr. Bergenstal proposed a “2 × 2” framework that incorporates people with diabetes and healthcare providers in a cross-section of medication and CGM use.
• Initiation of CGM earlier in the disease course was a topic of discussion in 2025, including its potential role in both T1D and T2D diagnosis. At ATTD, Profs. Chantal Mathieu and Tadej Battelino highlighted CGM’s growing diagnostic value, emphasizing that early glucose abnormalities can be detected and addressed long before traditional markers shift. Prof. Mathieu described how CGM-derived patterns that can help stratify progression risk in stage 2 T1D. Prof. Battelino, meanwhile, asserted that CGM should be routinely offered to those with T2D and those with prediabetes, as early glucose abnormalities can be identified and addressed with lifestyle or pharmacologic interventions. He further proposed that CGM could soon become an independent diagnostic marker for dysglycemia, either by establishing specific glucose thresholds for prediabetes and T2D or by incorporating dynamic markers of glycemic variability. Both noted that although formal guidance has yet to catch up, “we have an unwritten consensus already” on the value of initiating CGM as early as possible.
• OTC CGM ended its first full year of availability in the US. While commentary on uptake of these devices has been sparse, Dexcom presented early Stelo real-world engagement data at ADA and Abbott expanded Lingo availability to Walmart, marking the first major brick-and-mortar OTC rollout and an important step for accessibility.
• Continuous ketone monitoring (CKM) platforms signal a shift toward multi-analyte sensing that could redefine metabolic monitoring. At ADA, Dr. Jennifer Sherr presented new pivotal data on Abbott’s dual glucose-ketone (DGK) sensor, demonstrating that ketone levels can rise independently from glucose and highlighting why real-time dual sensing may help identify infusion-set failures among AID users and proactively prompt ketosis management. In its product theater at ADA, Abbott also previewed new data on its multi-analyte sensor, with early clinical evidence suggesting improved pattern recognition and earlier detection of DKA risk compared to glucose-only monitoring. Many have also highlighted the sensor’s potential to safely bring the SGLT-2 inhibitor drug class to people with T1D safely. Momentum is already building across the industry, with five pump partners already confirming it would integrate with the DGK: (i) Sequel’s twiist; (ii) Tandem’s t:slim X2 and Mobi with Control-IQ+; (iii) Beta Bionics’ iLet; (iv) Ypsomed’s mylife Loop; and (v) Insulet’s Omnipod 5.

2. AID uptake continues to grow with guidance on initiation at diagnosis and more systems available to the T2D population in the US and Europe

AID continued its strong growth throughout 2025 with several major regulatory clearances and launches of CGM integrations that will provide more choice for people with diabetes. We estimated that nearly 1.6 million people worldwide use AID systems at the end of 3Q25 (see graph below). Looking ahead, we see no signs of the AID market slowing down, as three AID systems have now received FDA clearance for people with T2D in the US (Omnipod 5, Control-IQ+, and MiniMed 780G), and the EU added MiniMed 780G to its cleared AID in T2D armamentarium (more on this below). While barriers related to access, continued challenges with exercise, prescriber bias, and difficulty with implementation within clinic workflows (particularly in primary care clinics) may impede broader uptake, we are hopeful that expanding interoperability will be able to better meet the unique needs of people with diabetes and enable more people to achieve improved outcomes. Furthermore, we are optimistic that strengthening ADA Standards of Care now designating AID systems as “the preferred insulin delivery system” for all people with T1D, as well as for adults and children with T2D who are currently using MDI, insulin pumps, or sensor-augmented pump therapy.

Estimated Global AID Userbase (3Q17-3Q25)

Source: Close Concerns Knowledgebase

• People with T2D in the US and EU were clear winners in the AID landscape in 2025. The first AID system to receive FDA clearance for the population, Omnipod 5 (August 2024), took advantage of its head start in the population and took the US by storm. Since then, up to 35% of new quarterly US starts have come from people with T2D and the company has focused on “taking the science to the street” by educating endocrinologists and PCPs on the latest evidence and treatment standards, and field teams are being equipped for peer-to-peer education and serving as “AID evangelists” to drive adoption in T2D. While Insulet worked on bringing more patients with T2D into the AID fold, two additional AID systems in the US received clearance for use in adults with T2D in 2025: Tandem’s updated Control-IQ+ algorithm in February and Medtronic’s MiniMed 780G in September. MiniMed 780G also received CE-Marking for use in T2D in July. Both companies have plenty of room left to begin taking share – estimates continue to place AID penetration among the US intensive insulin-using population with T2D (~2.5 million people) at only ~5%. Tandem is set to begin expanding its T2D commercial strategy beyond pilot programs. Early commercialization efforts have suggested that T2D users generally prefer t:slim X2 over Mobi, gravitating to the pump’s screen display and 300-unit reservoir size compared to the 200-unit reservoir of the screen-less Tandem Mobi.
• Sequel Med Tech launched its system in 2025: Sequel’s twiist, which is the first FDA-cleared AID system to use an algorithm based on Tidepool Loop, entered a full commercial launch in early fall. The system is also the first FDA-cleared system to offer direct control through the Apple Watch and offers the broadest customizable correction range of any commercial system (87-180 mg/dL).
  • Meanwhile, CamDiab’s CamAPS FX, which will be the first FDA-cleared algorithm for pregnancy in T1D, has not yet launched in the US despite the algorithm receiving FDA clearance in 2024. This is due to the lack of an FDA-cleared insulin pump integrated with CamAPS FX in the US offering integration with CGMs Dexcom G6 and FreeStyle Libre 3. Ypsomed submitted its mylife YpsoPump for FDA clearance in the beginning of 2024, but we have not heard any regulatory updates since.
• Interoperability continued to expand in 2025.
  • Insulet has launched FreeStyle Libre 2 Plus integration for users in several markets, including the UK, Netherlands, US, Italy, Belgium, Switzerland, the Nordic countries, and Australia. It also integrated Omnipod 5 with Dexcom G7 in at least a half dozen international markets: Sweden, Denmark, Finland, and Italy, the UK, and the Netherlands. In the US, Omnipod 5 integrated with Dexcom G7 15 Day at its launch in December 2025. Looking ahead, the company plans to integrate Omnipod 5 with FreeStyle Libre 3 Plus in 1H26, marking compatibility with every major CGM in the US.
  • Tandem launched t:slim X2 integration with FreeStyle Libre 3 Plus in the US in October, with an international launch of the integration and integration with Tandem Mobi expected to come next year – slightly delayed compared to expectations, as an international launch of the compatibility was initially planned for 3Q25. The company continues to work on compatibility with the G7 15 Day.
  • Beta Bionics’s iLet integrated with the G7 15 Day at launch.
  • Sequel launched in the US with FreeStyle Libre 3 Plus integration and Eversense 365’s integration with twiist is its first entrance into AID systems.
  • While Medtronic still does not integrate MiniMed 780G with any non-Medtronic CGMs, it added two new sensors to the MiniMed 780G platform’s repertoire in the US in recent months: Simplera Sync and the Abbott-developed Instinct. Both sensors have already seen strong order rates, and Medtronic is optimistic that their availability will drive MiniMed 780G adoption in the US. Simplera Sync availability expanded across the EU in 2025, now available in approximately 30 countries, and has fueled OUS MiniMed 780G growth.
• We continued to see new data of AID systems in expanded populations, including pregnancy and very young children.
  • On AID use during pregnancy, Tandem’s CIRCUIT trial (n=88) for t:slim X2 in pregnant women with T1D was published in JAMA Network in October. Those using t:slim X2 during pregnancy achieved significantly higher mean Time in Pregnancy Range (TIPR, 63-140 mg/dL) than those continuing standard care (CGM; 65% vs. 50%), supporting the efficacy and safety of the system’s use. An immediate improvement to TIPR was seen within a week of initiating Control-IQ, rising from a median of ~55% to nearly 70%. TIPR rose to ~75% in the final few weeks of gestation. Exploratory outcomes from CIRCUIT suggested additional maternal benefits with t:slim X2 use, including: (i) lower A1c levels (0.4 points lower at 34 weeks than standard care); (ii) reduced preeclampsia rates (14% versus 25%); and (iii) lower total insulin requirements (by ~28 units/day).
    • Medtronic received CE-Mark approval for expanded use of MiniMed 780G in pregnancy in July, the first since CamDiab’s CamAPS FX in 2020. In the US, Medtronic has said that it expects to file an FDA submission to remove a warning for use in pregnancy, though updates have been few in recent months.
  • On AID in preschoolers, Dr. Klemen Dovč (University of Ljubljana, Slovenia) presented findings from the extension phase of Medtronic’s LENNY trial at ATTD 2025, in which Simplera Sync demonstrated non-inferiority to the Guardian 4 sensor in preschoolers – the A1c difference between groups was not statistically significant (7.3% vs. 7.2%), and there was no clinically significant difference in TIR between treatments (70% vs. 69%). At ATTD 2025, Dr. Jolien De Meulemeester (KU Leuven, Belgium) presented results of a 12-month prospective, observational study of MiniMed 780G in those aged 2-6 years. The study showed median TIR increased 10% (+2.3 hours/day) from 57% at baseline to 66% at 12 months, with equivalent gains to TITR (from 36% to 46%). Median A1c decreased 0.3% from 7.6% at baseline to 7.3% at 12 months, and school and work absenteeism tended to decrease. In July, Medtronic received CE-Mark approval for MiniMed 780G use in those aged 2+ years.
    • Also at ATTD 2025, Dr. Torben Biester (Auf Der Bult, Germany) shared findings from a single-center, prospective study (n=27) evaluating the impact of switching preschool-aged children (younger than six years old) with T1D from predictive low glucose management systems to the mylife Loop AID system. TIR increased 2.9 hours/day from 52% to 64% after three months, and A1c decreased significantly from 7.8% at baseline to 6.8% in the same timeframe; reductions remained stable at six months. Another study published in DT&T in November showed that within the first month of CamAPS FX use, TIR rose by ~11%, (from 54% to 64-65%) and A1c levels dropped 0.9% (from 7.8% to ~7.0%).

3. Closing the loop: Studies evaluating the safety and efficacy of FCL algorithms in T1D and T2D march on; FCL-like use grows in HCL users who don’t bolus

In 2025, the push to "close the loop" in automated insulin delivery continued to gather momentum, with several new studies and updates from major diabetes tech companies on upcoming feasibility and pivotal trials.

• Several FCL algorithms made significant strides, with new feasibility data and commitments from the industry to advance their systems.
  • CamAPS HX: A randomized crossover study published by DT&T in June compared the FCL CamAPS HX algorithm to sensor-augmented pump (SAP) therapy among adolescents with T1D and above-target A1c (n=24). The results showed that FCL use resulted in a significantly higher TIR compared to SAP (45% vs. 32%), translating to a 3.1-hour daily difference. This improvement was driven by a reduction in Time above 250 mg/dL, which was 7% lower with FCL (29% vs. 40% with SAP). Time below Range (TBR) was similar between groups (2.8% for FCL vs. 3.0% for SAP). However, there was no significant difference in A1c (8.6% with FCL vs. 8.9% with SAP).
  • EVOLUTION Study: Insulet announced at its Investor Day in November that it plans to launch its FCL AID system in 2028. Insulet's initial focus will be on the T2D basal-bolus population, with expansion planned for basal-only patients. The EVOLUTION2 feasibility study is expected to begin enrollment in 2026, with a regulatory submission anticipated in 2027.
  • FCL@Home Study: At ATTD 2025, Dr. Laya Ekhlaspour (UCSF) presented feasibility results from the FCL neural-net AIDANET algorithm (n=36). Among participants with an A1c <8.0%, FCL was noninferior to usual care (68% vs. 66% TIR). In those with A1c >8.0%, FCL demonstrated significant improvements, with 13% greater TIR (+3.2 hours/day) compared to usual care (62% vs. 49%). Dr. Erin Cobry (University of Colorado) later presented daytime and nighttime results at ADA 2025, where AIDANET use showed non-inferiority to HCL care for daytime (58% vs. 56% TIR), and significantly greater TIR during nighttime use (76% vs. 64%). Also at ATTD 2025, Dr. Boris Kovatchev (University of Virginia) presented promising early results from a study combining AIDANET with a glucose pretrained transformer for automated bolus priming (Bolus GPT). In the first six participants, this combination delivered a 2.2-hour/day improvement in TIR, reaching 76% compared to 67% with AIDANET alone. TITR was also improved, reaching 53% with Bolus GPT and AIDANET versus 46% with AIDANET alone.
  • Tandem Freedom: Tandem’s clinical trial for its FCL AID system completed in 2Q25, with a pivotal study expected to start in 2026. Dr. Tom Wilkinson (University of Otago) presented data on the second-generation Tandem Freedom FCL system at ATTD-Asia 2025, which showed strong overnight glycemic outcomes. The median TIR was 61%, an improvement from 56% during the run-in period, with overnight TIR nearly reaching 100% (96%). The system responded quickly to meals, with most postprandial insulin was delivered within two hours for all meals despite the lack of user-initiated announcements.
  • Medtronic Vivera: Medtronic announced in 3Q25 that the FDA had authorized the initiation of a US pivotal trial for its third-generation FCL algorithm, "Vivera."
  • Inreda AP: DT&T published a qualitative follow-up study in October on the FREE 1 trial, which evaluated Inreda’s bi-hormonal FCL system that delivers both insulin and glucagon. Interviews with participants (n=12) revealed that many found the system transformative, easing the burden of carbohydrate counting. However, some users expressed frustration with the device’s complexity, including daily glucagon changes, two sensors, and frequent alarms. Overall, participants reported feeling less burdened by diabetes, reflecting the strong quantitative outcomes (~80% TIR) from the FREE 1 trial.
• Several companies also demonstrated the effectiveness of their AID systems with simplified meal reporting, further reducing the burden on users.
  • Control-IQ: Dr. Laurel Messer (Tandem) highlighted a 12-month single-center study of Control-IQ users at EASD 2025, with the majority relying on AutoBolus (>90%). The study showed a 19% increase in TIR and a 1.6% reduction in A1c from baseline.
  • MiniMed 780G: Dr. Jennifer McVean (Medtronic) presented real-world outcomes at ADA 2025 from the MiniMed 780G on days without user-initiated boluses (n=54,553). The system achieved a mean TIR of 71%, with a mean TITR of 44%. Among non-recommended settings users (n=41,830), 37% met the triple composite endpoint: (i) GMI <7.0%; (ii) TIR >70%; and (iii) TBR <4.0%. In comparison, 62% of recommended settings users (n=12,723) met this endpoint.
    • At EASD 2025, Dr. Salvatore Scirè Calabrisotto (University of Catania, Italy) compared the response of Medtronic MiniMed 780G and Tandem Control-IQ to unannounced meals in a randomized crossover study (n=20). MiniMed 780G had a lower mean peak (~200 mg/dL) compared to Control-IQ (~220 mg/dL). Both systems performed similarly in terms of TIR and TITR with announced meals, though MiniMed 780G handled unannounced meals slightly better, suggesting that PID-based algorithms may be more effective in such situations.
  • Omnipod 5: Dr. Sean Oser (University of Colorado) presented at ADA 2025 data showing that while users who bolused more frequently achieved higher TIR (74% with >4 boluses/day vs. 62% with <1 bolus/day), those relying on simplified carbohydrate counting (using just five main carbohydrate values) achieved comparable outcomes to those using precise carbohydrate counting (69% vs. 73% TIR).
  • Open-source AID: A study conducted in China (n=32) with adults with T1D alternated between two weeks of open- and closed-loop use while employing a non-carbohydrate counting meal bolus strategy. After a one-week run-in period, participants achieved ≥70% TIR, with significantly higher TIR (79%) during closed-loop use compared to open-loop (not specified).
• Faster insulins and AID system compatibility. While the FDA cleared fast-acting insulins for use with all insulin pumps in 2021, it required that individual pump manufacturers demonstrate compatibility with AID system algorithms – in 2025, several significant updates on this front were made. In September, Tandem announced FDA clearance to use its t:slim X2 with Control-IQ+ in combination with Lilly’s fast-acting insulin, Lyumjev (insulin lispro-aabc), becoming the first AID system cleared for use with Lyumjev in the US. Meanwhile, Medtronic submitted for FDA clearance of the MiniMed 780G with fast-acting insulins (Lyumjev, Fiasp, Merilog) in 1Q25. Additionally, Sequel entered a co-development agreement with Arecor in September to pair its ultra-rapid insulin AT278 (500 U/mL) with Sequel’s Twiist AID system. This collaboration aims to enable next-generation AID systems with longer wear times and miniaturization potential, especially for individuals with high daily insulin needs.
• Bi-hormonal AID systems. In 3Q25, Beta Bionics reported progress on its bi-hormonal AID system, which delivers both insulin and glucagon. The company completed its first pharmacokinetic-pharmacodynamic (PK-PD) bridging trial for its proprietary glucagon, marking a key milestone. Results met expectations, allowing the company to proceed with a human feasibility study for the dual-hormone system, scheduled for 4Q25. This will precede pivotal trials and regulatory submissions for both glucagon and the integrated device.

4. TITR, Time in Normoglycemia, Time in Happiness? Tighter glycemic management gains traction as debate on its name (and ideal range) emerges

The conversation around Time in Tight Range (TITR; 70-140 mg/dL) moved further into the spotlight in 2025. As part of it, clinicians debated the benefits of tighter management against the clinical and psychosocial challenges of demanding even more precision than with TIR (70-180 mg/dL), and whether TITR should be a primary goal or a secondary metric. This prompted some to suggest a parallel focus with TIR and TITR to balance clinical goals with real-world burden.

• At ADA, Prof. Tadej Battelino (University of Ljubljana, Solvenia) delivered a strong push to replace A1c with CGM-derived metrics, arguing that TIR and TITR outperform A1c in predicting complications and detecting early dysglycemia. He highlighted data linking TITR to reductions in mortality, albuminuria, and retinopathy in T1D and T2D, arguing that it captures early physiologic deterioration that A1c can fail to recognize. Prof. Battelino also introduced the name “TING” – Time in Normoglycemia – explaining that the new name reflects the goal to achieve “normal glycemia.”
• At ATTD, qualitative work from people with diabetes and caregivers revealed enthusiasm for TITR’s potential but concern about burden, burnout, and feasibility, prompting calls for “Time in Happiness” as an alternative goal. Dr. Molly Tanenbaum (Stanford University) shared survey and interview data showing that while about one-third of respondents were open to TITR and many in this group were already informally using 70–140 mg/dL targets with AID systems, roughly two-thirds expressed hesitancy, citing fears of increased hypoglycemia and lack of tools or algorithm performance to realistically sustain tighter ranges. Some parents and athletes worried that TITR-based targets could constrain food choices or safe exercise, while others emphasized that any new goal must be phased in and accompanied by clear evidence of benefit. One respondent’s suggestion to prioritize “Time in Happiness” as an alternative to conventional glycemic metrics captured the emotional impact: tighter numbers alone are not enough if they come at great expense to quality of life.
• A lively debate at ATTD highlighted a key question: should TITR be a core clinical target today or remain a research metric for select groups? Arguing in favor, Dr. Anders Carlson (International Diabetes Center) described TITR as a powerful early-warning signal and complication predictor, citing data linking incremental decreases in TITR with higher risks of retinopathy, microvascular complications, and cardiovascular mortality, and proposing that TITR may detect dysglycemia earlier than TIR can. He outlined patient profiles where TITR might be especially useful, including newly diagnosed individuals aiming for physiologic normoglycemia and those with rising A1c levels driven by high Time in 140-180 mg/dL.
  • In contrast, Dr. Jeremy Pettus (UCSD) argued that TIR remains a more patient-friendly target, warning that current technology is not yet capable of consistently delivering this tight management without increased hypoglycemia and burden. He said pushing TITR as a primary goal risks demotivating patients already struggling to achieve TIR. He supported TITR as a valuable research metric but cautioned against premature clinical adoption.
• TITR moved from a niche metric to a practical benchmark in 2025, with multiple studies showing that it can improve meaningfully across AID systems. Namely, we saw large real-world datasets demonstrating that modern algorithms can raise TITR by two to three hours per day while maintaining low hypoglycemia and reduced burden. These findings suggest that when people access advanced AID systems and use optimized settings, tight glycemic profiles are achievable.
  • With MiniMed 780G, a cohort of users without user-initiated boluses (n=54,554) showed that mean TITR still reached 44% overall and nearly 50% among users on recommended settings with the system. Elsewhere, Dr. Jennifer McVean (Medtronic) presented three-year real-world evidence (n=1,145) from MiniMed 780G users (≥16 years old) across Europe, the Middle East, and Africa, showing sustained glycemic improvement, with TITR rising from 40% at baseline to 54% and remaining over 50% through 36 months. In yet another MiniMed 780G analysis (n=40,975) stratified by Area Deprivation Index, Dr. McVean found that TITR averaged ~47% across all socioeconomic quartiles, with users on recommended settings reaching ~52% TITR and higher rates of target achievement.
  • With Tandem’s Control-IQ, real-world data in children under 11 years showed that both children under six and those six to 10 years old achieved significant and sustained TITR gains by six months, with earlier initiation after diagnosis associated with greater TITR and lower A1c levels. The two-year INRANGE study (n=473) of Tandem’s Control-IQ echoed this durability in adults with T1D, where TITR increased from 37% at baseline to 45-46% at 12 and 24 months. The number of participants achieving TITR over 50% nearly doubled, alongside sustained A1c improved and reduced hypoglycemia.
• The evidence base supporting TITR as a meaningful metric for people with T2D not using insulin continued to expand. In the UNITE RCT of adults with T2D (n=124) on non-insulin therapy initiating Dexcom G7, TITR increased 4.3 hours/day in the nutrition-focused education arm (from 16% to 34%) and 2.9 hours/day in the self-directed arm (from 23% to 35%) over two months, with minimal Time below Range (TBR), significant TIR and A1c improvements, and added dietary quality gains in the nutrition-focused group. Dexcom’s first real-world analysis (n=61,085) of Stelo users expanded this picture into the OTC landscape. There were notable differences to TITR achieved by individuals without diabetes, with prediabetes, and with non-insulin T2D (baseline TIR >70%), at ~93%, ~86%, and ~65%, respectively. These data highlighted TITR’s sensitivity to subtle dysglycemia that standard TIR metrics might fail to recognize. Regardless, in the highest-risk subgroup (people with T2D and baseline TIR ≤70%) TITR still improved from 12% to 20% (+1.9 hours/day) with 30 days of Stelo use, further suggesting that visibility alone can help guide users toward tighter glucose management.

5. Diabetes technology in pregnancy: Evolving global guidelines and the search for more data

Diabetes in pregnancy was defined in 2025 by new global guidelines and regulatory milestones, along with real-world and clinical evidence supporting both CGM and AID use across T1D and GDM. These developments highlighted AID and CGM as powerful tools in the management of T1D pregnancy, while also highlighting the need for pregnancy-specific algorithms, clinician training, and thoughtful implementation.

• 2025 guidelines aligned on expanding technology and structured glycemic management in pregnancy, with the ADA advancing AID use and the World Health Organization (WHO) issuing its first global diabetes in pregnancy care framework. Conferences throughout the year became grounds for clinician education on the evolving guidelines for the population. At ADA, Dr. Sarit Polsky (University of Colorado) outlined extensive updates to the ADA Standards of Care’s pregnancy chapter that recommended (and reiterated in the 2026 iteration published earlier this month) that clinicians consider AID with pregnancy-specific algorithm for individuals with T1D, grounded in evidence from AiDAPT and CRISTAL studies. She emphasized that AID use must occur within experienced provider teams alongside foundational steps of reviewing medications throughout pregnancy and tightly coordinating care. Complementing this, Dr. Rita Kalyani (Chief Scientific and Medical Officer, ADA) promoted Recommendation 7.18 from the ADA 2025 Standards of Care, which formally recommends CGM use for T1D pregnancy. Globally, the WHO published a comprehensive set of guidelines for diabetes care during pregnancy. The guidelines introduced three core practices to guide care for women with diabetes during pregnancy: (i) individualized lifestyle guidance; (ii) education on maternal-fetal health effects; and (iii) access to specialized diabetes-pregnancy teams. Detailed recommendations were issued for glucose monitoring and establishing glycemic targets, including the use of CGM for T1D where available and BGM-based monitoring for T2D and GDM in most settings due to resource constraints. Together, the 2025 ADA and WHO guidelines highlight a growing global consensus that pregnancy care must move forward technology-supported approaches that make sense in the pregnant women’s lives.
• In July, Medtronic received CE-Mark for expanded indications including pregnancy, which launched in the fall. This is the first new AID pregnancy clearance in Europe since CamDiab’s CamAPS FX in 2020. The authorization, supported by data from the CRISTAL trial, positioned MiniMed 780G as a second option for pregnant women with diabetes. Notably, this clearance gives pregnant patients in Europe a choice between two regulated AID systems for the first time, representing meaningful progress in maternal glycemic management. Medtronic has also stated it expects to pursue removal of the pregnancy contraindication in the US, raising the possibility of expanded access beyond Europe in the coming year.
• NHS England launched the first nationwide pregnancy-specific AID initiative, expanding access to the technology in T1D pregnancy. In September, NHS England announced a national rollout of a pregnancy-tailored AID system for women with T1D who are pregnant or planning pregnancy. The program was backed by £3.7M (~$5M) in initial funding as part of a broader £60M (~$81M) initiative. The initiative aims to enable women to reach the tighter pregnancy glucose targets with the AID system and remote monitoring through NHS data infrastructure, aiming to reduce adverse maternal and neonatal outcomes in T1D pregnancy. With more than 600 women enrolled by the beginning of September 2025, this rollout positions the UK as the first country to systemically deploy pregnancy-specific AID use at a national level.
• New trials across T1D and GDM strengthened evidence for CGM to improve maternal and neonatal outcomes. At ADA, Dr. Karen Elkind-Hirsch (Dexcom) shared results from the Steady Sugar RCT (n=120), where early CGM use during pregnancy led to lower unscheduled C-sections (20% vs. 44%), fewer preterm births (7% vs. 18%), and better neonatal outcomes including reductions in LGA births (5% vs. 18%) and NICU admissions (23% vs. 45%). CGM is also received positively by pregnant women – Ms. Rachel Salzman (Weill Cornell) highlighted strong patient satisfaction and high adherence for CGM (76% wore CGM ≥70% of the time) in Weill Cornell’s virtual GDM program. At EASD, Prof. Tina Linder (Medical University of Vienna, Austria) presented results from the international GRACE RCT (n=375), showing that CGM use in GDM significantly reduced LGA rates (2.5% vs. 10.3% with BGM) and improved late-pregnancy glycemia. Prof. Helen Murphy (University of East Anglia, UK) echoed CGM’s role in identifying dysglycemia and GDM earlier in gestation and expressed optimism about forthcoming results from the MAGiC study and its collaboration with GLAM, which she hopes will show that abnormal glucose patterns are already detectable in the first trimester.
• We also saw more real-world data for AID use during T1D pregnancy. At ADA, Dr. Emily Szmuilowicz (Northwestern University) explained that most commercial systems struggle with responding to the rapid progression of insulin resistance during gestation (~250% of pre-pregnancy insulin dose by 35 weeks) and pregnancy-specific fasting targets (70-95 mg/dL). To support optimal outcomes, she outlined trimester-specific adjustments across systems, including: (i) pregnancy-tailored glucose targets (i.e., Time in Pregnancy Range); (ii) aggressive insulin-carbohydrate ratios; (iii) careful pre-bolus timing; and (iv) repeated correction factor updates. At ATTD, Dr. Emma Wilmot described a “watershed moment” for AID adoption in T1D pregnancy, citing 100% uptake in her clinic. At Ypsomed’s sponsored session, Prof. Helen Murphy presented new CamAPS FX pregnancy data demonstrating 1.8% A1c reductions from an undisclosed baseline and 63% of users reaching <6% A1c, alongside healthcare cost reductions and declines in preeclampsia.

6. Inpatient CGM use demonstrates positive impact on glycemia and re-hospitalization rates as accuracy shows mixed bag

Following the less-than-promising results of the TIGHT study in 2024, 2025 was a consequential year for data supporting the technology’s use in the hospital setting. For reference, the highly-anticipated TIGHT study ultimately found no significant difference in mean glucose with CGM use between the intensively managed and standard management groups, though some have since said that this does not mean CGM is ineffective in the inpatient setting – rather, the 90-130 mg/dL target may not be realistic in “real life.” Regardless, support for the use of CGM and decision support systems grew throughout the year.

• Evidence on inpatient CGM accuracy accumulated in 2025:
  • At EASD 2025, Prof. Mikkel Olsen (Steno Diabetes Center Copenhagen) presented the DIETEC trial (n=166), which showed that inpatient CGM use increased TIR by 15 percentage points (from 63% to 78%) in patients with T2D. Patients using CGM achieved steady improvements in TIR by discharge, while those using BGM plateaued at 60%. Additionally, CGM use was linked to a 24% reduction in hospital complications, particularly infections. Prof. Olsen acknowledged that accuracy is strongest in non-ICU settings and more variable in ICU patients, reinforcing the need that many in the ICU may need more attention to glycemic health. He called for a consensus framework to define patient selection criteria and glycemic targets, as well as for better integration of CGM data into EHRs.
  • Dr. Lyn Hopkinson and colleagues from MedStar Health presented a real-world study at ADCES 2025 showing a clinically significant 79% reduction in hypoglycemic events with CGM use. This study found that CGM provided more accurate readings in patients with blood sugar below 85 mg/dL compared to BGM, supporting its use in detecting and managing hypoglycemia.
  • In a study on ICU patients published in DT&T in May, Dr. Jesica Baran (University of Washington) et al. analyzed the accuracy of the Dexcom G7. They found that the MARD in ICU settings was slightly higher (16%) than in outpatient settings, but similar to the MARD observed in non-ICU hospitalized patients (15%). This data underscores the potential for CGM to be useful in critically ill patients, though accuracy remains more variable in such settings. Elsewhere, Dr. Guillermo Umpierrez (Emory University) teased an ongoing RCT comparing Dexcom G7 with POC glucose testing in hospitalized patients with T2D.
  • Dr. Magdalena Bogun (Columbia University) presented an observational study (n=163) on the use of CGM in DKA management with IV insulin infusion at EASD 2025. Although CGM sensors showed a MARD of 17.4% during IV insulin treatment — above the typical 10% threshold for outpatient use — the study's Clarke Error Grid analysis indicated that 99% of paired values were within acceptable ranges (Zones A/B) during treatment and 96% post-resolution. The study also found that CGM use resulted in significantly fewer POC tests compared to standard care (five vs. 12 tests, p<0.0001). However, the difference in median hospital stay (120 hours for CGM vs. 99 hours for standard care) was marginally significant, potentially making a noticeable difference to patients.
• Clinicians and guidelines increasingly support the noninferiority of some CGMs to point-of-care (POC) BGM for inpatient glucose management. Prof. Spiros Fourlanos (University of Melbourne, Australia) provided an overview of the growing use of CGM in hospitals, highlighting both its clinical benefits and the challenges posed by real-world implementation. He discussed data from several RCTs, including the DIATEC study presented at EASD 2025. Guidelines from major organizations, including the ADA and recent Australian standards, now endorse CGM use in non-critical care patients, provided it is accompanied by POC monitoring. He emphasized the need for practical rules to ensure safe implementation, including to: (i) remove CGM only if the patient cannot participate (e.g., unconsciousness); (ii) defer but do not necessarily remove during periods of hemodynamic instability; and (iii) otherwise, use CGM as a patient prompt for confirmation POC checks.
• Some clinicians are also looking forward to greater inpatient implementation of other diabetes technologies, including AID and decision support systems. At Diabetes UK 2025, Dr. Hood Thabit (Manchester University NHS Foundation Trust) discussed the potential of decision support software in glycemic management, though he noted the lack of robust RCT evidence. He also highlighted studies showing the benefits of FCL AID systems, which can reduce staff workload and improve glycemic control. Dr. Thabit stressed that successful implementation would require workflow adaptations and training, especially for non-diabetes specialists. Dr. Bruce Bode noted that new CMS mandates in the U.S., effective January 2026, would require hospitals to report severe hypoglycemic and hyperglycemic events, providing additional incentives for hospitals to address these issues proactively.
  • In a bid to support the use of inpatient diabetes decision support systems, Glooko announced its acquisition of Monarch Medical Technologies, the maker of the EndoTool Glucose Management System, in September. EndoTool is an FDA-cleared software that provides patient-specific inpatient insulin dosing recommendations aimed at reducing hypoglycemia risk and standardizing outcomes across critical care units. Glooko, which has traditionally focused on outpatient remote monitoring, will expand its platform to integrate more hospital-based features, providing tools for inpatient insulin titration based on individual patient needs, including insulin sensitivity and comorbidities.
  • Several companies and clinicians indicated 2026 will see broader uptake of these technologies with the goal of proactively addressing the issue of severe hypoglycemia and hyperglycemic events, as the CMS will begin mandating hospitals report the events beginning January 2026. Financial penalties for failing to report these events have not yet been disclosed, but Dr. Bruce Bode predicted they will drive uptake of tools like Glytec’s Glucommander, which expanded to more hospital systems in 2025.

7. The many faces of AI: Clinical applications, AI in research

AI is increasingly being applied in clinical care, particularly in diabetes management, drug discovery, and disease prediction. Throughout the year, experts emphasized its potential but also advise caution, particularly around issues of accuracy, data privacy, and human oversight.

• AI is transforming the way patients engage with their glycemic and nutritional data, helping contextualize it among other documented lifestyle inputs. Several companies are leading the way with innovative applications:
  • Dexcom integrated CGM data with FriskaAi’s health management platform in August, offering real-time alerts, personal care recommendations, and clinician reports. Dexcom also launched AI-powered features like Food Logging (July) and Weekly Insights on its Stelo platform (December 2024), which provides GenAI-powered recommendations on diet, exercise, and sleep for users.
  • Roche continued to roll out its AI-powered Accu-Chek SmartGuide Predict app, providing users with AI-powered glucose level predictions, alerts for low glucose risk, and recommendations for preventing hypoglycemia. The company presented a case study on the app’s use and these predictive features at the Swiss Economic Forum in June 2025.
  • Omada Health launched Meal Map in October, an AI tool that analyzes the nutrient density of meals and offers personalized dietary recommendations. The new tool builds on Omada’s AI-powered “Nutritional Intelligence” suite, which includes the recently-launched OmadaSpark, and in an internal pilot study (n=1,000) the tool was associated with higher engagement in meal tracking compared to traditional calorie-focused approaches.
  • Trinity Biotech unveiled plans in July for CGM+, an AI-powered CGM that is designed to track users’ glucose, heart activity, body temperature, and physical activity continuously. Trinity anticipates a commercial launch in 2026.
  • Signos announced the launch of its AI-driven glucose monitoring platform for weight management in August, combining Dexcom Stelo data with a behavioral AI mobile app to deliver real-time, personal lifestyle recommendations. The company is conducting a large clinical trial to study its effects.
  • Twin Health saw Cleveland Clinic-led RCT data published in NEJM Catalyst in which the company’s Twin Precision Treatment significantly outperformed standard care for T2D. A1c fell 1.3% after one year, significantly greater than the 0.3% reduction to 6.9% with usual care, and 71% of participants reached A1c <6.5% at one year vs. just 2% of those receiving standard care.
  • Additionally, at the MDUFA VI public meeting, FDA Commissioner Dr. Martin Makary highlighted the FDA’s plans to optimize its application processing by digitizing the entire process, including with significant uptake (“thousands” of unique daily users) in the use of ELSA, its AI-powered reviewing tool.
• Yet another application of AI increasingly used by companies is in its role to accelerate drug development. Many have already announced partnerships with several AI-enabled companies to support their innovative pipelines, aiming to reduce timelines and improve the pace of candidate selection:
  • Lilly has entered into at least a half dozen AI-based partnerships, including with NVIDIA, TuneLab, Superluminal, Atomwise, Genetic Leap, Isomorphic Labs, and an expanded partnership with Purdue University, to speed up drug discovery.
  • Novo Nordisk has similarly appeared to have invested heavily in AI-enabled drug discovery and telehealth collaborations – the company has also partnered with NVIDIA, with Fangzhou on a Smart Healthcare Platform, and with Deep Apple Therapeutics  to use AI-powered biological pocket extraction and protein movement modeling to identify and advance novel candidates for a broad range of diseases.
  • Roche, expanding on its “Lab-in-the-Loop” approach that was a focus of its 2024 Digitalization Day, shared at its 2025 Pharma Day that its digitalization and AI strategies now includes greater use of generative AI to support R&D by accelerating protocol design, data collection, and study reporting. Roche’s “Lab-in-the-Loop” AI/machine learning model has already cut report generation time by >60%, increased screening yield by >10%, and reduced capital expenditures by making existing facilities more efficient.
  • Sanofi reported in November using AI to reduce preclinical discovery timelines by 30-50% and cut costs by 25-50%. AI also helped identify 10 new drug targets within a year. Additionally, AI is being used to prevent supply shortages across 60 sites.
• AI is also being leveraged for chronic disease monitoring and early detection and risk identification for:
  • Chronic kidney disease (CKD): Roche received CE-Mark approval for its Kidney Klinrisk Algorithm in October, launching the medical algorithm as part of a new CKD algorithm panel within Roche’s navify Algorithm Suite. The new CKD algorithm panel estimates the risk of kidney function decline in adults with CKD (G1-G4), diabetes, or hypertension, aiming to facilitate earlier risk assessments of patients and coordinated care across clinical teams.
  • T1D: The NIH funded in October the Multimodal AI for Type 1 Diabetes (MAI-T1D) project to apply AI to understand the mechanisms driving T1D onset, hopefully uncovering early biomarkers and prevention strategies. Speaking on AI’s applicability in early T1D pathology, Prof. Moshe Phillip (Schneider Children’s Medical Center, Israel) said at Keystone 2025 that while initiating CGM within a year of T1D diagnosis is associated with strong glycemic benefits, the technology will likely require AI-enabled analytical tools to be useful in monitoring pre-T1D staging.
  • Diabetic retinopathy (DR): AI tools for DR screening have been evaluated for longer than other conditions. Looking ahead, Ainnova Tech and Avant Technologies will be moving forward with a revised clinical trial protocol assessing the Vision AI platform for the early detection of DR leveraging AI to analyze fundus photos for retinal diseases. In addition to its high accuracy, Dr. Maria Cicinelli (IRCCS San Raffaele Scientific Institute, Italy) emphasized at EASD that AI-assisted screening can positively impact screening uptake by improving patient satisfaction, such as in children.
  • Liver fibrosis: AI-powered tools like Altimmune’s Liver Explore have shown promise in analyzing liver fibrosis reduction in clinical trials, demonstrating how AI can streamline disease monitoring and treatment decisions.
  • AI in lifestyle interventions and daily management: A phase 3 trial comparing AI-driven vs. human-led diabetes prevention programs (DPP) presented at DTM 2025 showed that AI-driven interventions were equally effective at reducing A1c and weight, suggesting that AI could become a viable alternative to traditional coaching. AI-based forecasting tools have shown potential in predicting hypoglycemia risk, enhancing patient safety, and Dr. Clara Mosquera-Lopez (Oregon Health & Science University) developed an AI algorithm for meal detection and insulin dosing that reduced Time above Range (TAR) by 11%. In a one-week outpatient study she presented at ADA 2025, the AI system showed performance similar to AID with fewer meal boluses, suggesting AI could reduce the burden of diabetes management.
  • Clinical trial screening: Dr. AJ Blood (Mass General Brigham) discussed a recently-published trial RAG-Enabled Clinical Trial Infrastructure for Inclusion Exclusion Review (n=4,476) demonstrating that an AI-assisted screening tool can improve both speed and accuracy of trial enrollment compared to manual review.
• AI’s integration into healthcare raises important questions and challenges, particularly in terms of patient-clinician relationships and ethical considerations. Dr. Jeffrey Moon (University of Pennsylvania) discussed at CEU 2025 how AI tools can reduce clinician burden, but warned against information overload. AI solutions like automated message triage and chatbots, if used responsibly, could enhance trust and reduce communication gaps. Dr. Joniqua Ceasar (University of Pennsylvania) discussed at AHA 2025 how AI-enabled prior authorization tools and low-cost telehealth models have the potential to overcome logistical barriers for both clinicians and patients. Meanwhile, Dr. Peter Jacobs discussed at ADA 2025 the potential of AI chatbots in mental health care, emphasizing the risks of overdependence on technology. Specifically, he said that while AI can improve access to mental health services, it may lack the depth and understanding of human therapists, leading to deceptive responses. At ADCES 2025, Ms. Ka Hei Karen Lau (Joslin Diabetes Center) explained that chatbot-generated responses to patient questions have been rated nearly four times higher than physicians for quality (79% versus 22%), and nearly 10 times higher for empathy (45% versus 5%), with over three-quarters of respondents preferring the chatbot’s answer. Challenges remain, however: Dr. Kushner at ATDC 2025 outlined some of these risks of AI in clinical care, particularly the danger of biased algorithms and misinterpreting patient behavior.

8. New ways of continuous monitoring: CKM, range-based feedback, and early disease insight

In 2025, continuous monitoring technologies moved beyond their tradition role in daily glucose management, with growing attention on risk prediction, simplified interpretation, and earlier disease prevention. Across major conferences and regulatory milestones, continuous data was increasingly framed as a tool to detect metabolic dysfunction sooner and extend meaningful insight to broader populations. Three areas stood out this year: (i) continuous ketone monitoring (CKM); (ii) the emergence of glucose range monitoring (GRM); and (iii) the potential use of CGM to support earlier identification and monitoring of presymptomatic, early-stage T1D.

• CKM emerged as a potential tool for DKA prevention and safer therapy use. CKM drew attention throughout 2025, driven by anticipation of Abbott’s dual glucose-ketone (DGK) sensor and growing clinical consensus that elevated ketone levels are often present before severe hyperglycemia. At ADA 2025, CKM was discussed in multiple high-profile sessions, including two powerhouse symposia dedicated to DKA risk and DGK. Dr. Jennifer Sherr (Yale University) presented pivotal and feasibility data on Abbott’s DGK sensor, demonstrating strong alignment with blood beta-hydroxybutyrate reference values across insulin pump suspension studies in adults and children. Notably, Dr. Sherr illustrated multiple cases in which ketone levels rose rapidly well before glucose exceeded 250 mg/dL, underscoring the limitations of glucose-only monitoring. Dr. Lori Laffel (Joslin Diabetes Center) highlighted rising DKA hospitalization rates and reviewed RCT evidence showing that blood ketone testing reduced emergency assessments by nearly 50% compared to urine testing, arguing that CKM could enable even earlier intervention at scale.
  • Complementing Abbott’s data, Dr. Ahmad Haider (McGill University) presented accuracy and feasibility results for SiBionics’ SiBio KS1 CKM. In adults with T1D using AID and undergoing ketogenic or intermittent fasting interventions, SiBio demonstrated “acceptable” accuracy versus capillary ketone testing. Results revealed that brief, asymptomatic elevations in ketones were relatively common, but brief. Dr. Haider emphasized that these findings support CKM’s role in acute risk detection and in improving understanding of real-world ketone dynamics during dietary variation.
  • More recently at ATTD-Asia 2025, Prof. Thomas Danne (Breakthrough T1D) discussed the importance of CKM adoption, saying that no individual hospitalized with DKA should be discharged without access to dual glucose-ketone monitoring. Dr. Jennifer Ngan (University of Melbourne, Australia) presented early insights from the run-in phase of the Australian PARTNER trial using Abbott’s CKM technology in people with T1D without acute illness. Dr. Ngan reported that most participants maintained normal ketone levels (<0.6 mmol/L) over two weeks of observation, with hyperglycemia being a poor predictor of ketosis and a trend toward lower carbohydrate intake among those with elevated ketone levels. These findings reinforced the concept that glucose and ketone trends frequently intersect in real-world settings, strengthening the case for real-time dual-analyte monitoring capabilities to support proactive DKA prevention and safer adjunctive therapy use.
• Glucose range monitoring became a new regulatory category designed to broaden access to continuous monitoring by prioritizing simplicity for users. In September 2025, the FDA granted its first De Novo authorization for a Glucose Range Monitoring System (GRMS) to Biolinq for Biolinq Shine, formally separating range-based glucose feedback from traditional continuous glucose monitoring. Unlike filament-based CGMs, Biolinq Shine uses a needle-free, intradermal microsensor array placed in the papillary dermis and delivers semi-quantitative, real-time glucose ranges via a color-coded LED display directly on the patch: (i) blue for in Range (70–180 mg/dL); (ii) yellow for above Range; and (iii) red for below Range.
  • At DTM 2025, Dr. Courtney Lias (FDA) highlighted Biolinq Shine’s authorization as a signal of FDA’s willingness to support novel device categories that deliver actionable insight without requiring numerical interpretation. Dr. Lias discussed how GRMS represents a regulatory shift toward expanding access and usability, complementing FDA’s momentum this year with expanded AID indications in T2D.
• CGM’s role in staging and monitoring of presymptomatic T1D was discussed. At ATTD-Asia 2025, Prof. Juliana Chan (Chinese University of Hong Kong) reinforced that while OGTT remains the diagnostic gold standard, CGM offers complementary biological insight, even among individuals classified as normoglycemic by fasting glucose or A1c. Prof. Chan emphasized that while CGM is not yet ready to replace OGTT as the standard, it may help refine staging when combined with factors such as biomarkers, genetic risk scores, and AI-driven insights.
  • Building on this concept, Dr. Viral Shah (Indiana University) introduced the CGM Dynamic Index (CDI) as a novel metric designed to capture the frequency, amplitude, and velocity of glycemic transitions, which static metrics may miss. Presented in the context of early dysglycemia and stage 2 T1D, CDI is now being validated in a Breakthrough T1D-funded longitudinal study tracking progression from stage 1 and 2 to stage 3 T1D, with the goal of determining whether CGM-derived dynamics can predict progression more accurately than A1c or OGTT alone.
  • At the population level, emerging longitudinal data further supported CGM’s potential role in early detection of T1D. A study from the Australian ENDIA cohort, led by Dr. Aveni Haynes (The Kids Research Institute Australia), showed that all children who progressed to clinical T1D had at least one blinded CGM session with time above 140 mg/dL >10% prior to diagnosis. In another perspective, a framework led by Prof. Nicholas Thomas (University of Exeter, UK) offered guidance for adults with islet autoantibody positivity, recommending A1c-led monitoring and selective CGM use in higher-risk or ambiguous cases, while warning that routine CGM may increase anxiety in lower-risk adults without clear clinical benefit. Collectively, these developments suggest that CGM is evolving into a contextual monitoring tool for presymptomatic T1D.
  • Reflecting momentum from 2025 evidence and discussions, the 2026 ADA Standards of Care updated Recommendation 3.2 to state that CGM metrics may be considered alongside A1c and OGTT in individuals with presymptomatic T1D, representing a formal recognition of CGM as complementary monitoring tool.

9. Digital health funding stabilizes in 2025 as capital focuses on AI-driven and workflow-focused platforms

In the digital health landscape, 2025 marked a rebound in total capital but reinforced the sector’s shift toward fewer, larger, and more AI-centered deals. Rock Health reported $9.9 billion invested across 351 deals in the first nine months of 2025, up from the $8.4 billion and $8.5 billion by that time in 2024 and 2023, respectively, but still well below record-high investments in 2022 and 2021. Deal volume continued to decline, reflecting investor consolidation around later-stage companies with demonstrated revenue and clinical outcomes. The average deal size increased to $28.1 million, up from $20.4 million in 2024. Nineteen mega-deals of more than $100 million accounted for nearly 40% of all capital. Meanwhile, over one-third of financings were for unlabeled rounds, a sign that startups are increasingly relying on capital to meet challenging benchmarks before progressing to traditional series raises. These trends collectively point to a more selective and outcomes-driven funding environment where AI-enabled workflow automation and value-based care continue to attract the strongest investor demand.

• Workflow and AI-powered tools dominated funding themes, signaling a shift away from disease treatment-focused digital solutions. Clinical and nonclinical workflow tools consisted of a combined 42% of total 2025 funding, with workflow mega-deals alone raising over $2.2 billion. Annual population health management funding rose tenfold to $1 billion by 3Q25, reflecting renewed investor alignment with prevention, risk stratification, and value-based care. AI-enabled products continued to command deal premiums.
• M&A activity increased as startups expand horizontally across the care continuum. More than 160 acquisitions were recorded through 3Q25, already surpassing 2024’s total of 121. This consolidation was driven by tougher performance expectations from investors and a shift toward end-to-end platform strategies. Rock Health noted that many private companies are now pursuing mega-rounds as a precursor to eventual public market entry.
• Across diabetes and metabolic care in 2025, digital health companies secured important regulatory milestones, expanded virtual obesity-care platform, and introduced next-generation sensors.
  • Omada Health strengthened its position in obesity and cardiometabolic care following its landmark initial public offering (IPO) in May. The company now reports 831,000 enrolled members (+53% from 3Q24) and $68 million in 3Q25 revenue (+49% from 3Q24). The company announced that its GLP-1 RA Care Track has expanded to include prescribing, an offering built on its “behavioral intelligence” from more than 100,000 GLP-1 RA users. New outcomes shared in 3Q25 showed that members who discontinued GLP-1 RA therapy but remained in Omada’s care platform maintained weight over 12 months, with 63% continuing to lose or maintain weight – much improved discontinuation outcomes compared to the ~11-12% weight regain typically seen in clinical trials.
  • Signos received FDA clearance for its AI-driven weight-management platform integrating Dexcom’s over-the-counter (OTC) CGM Stelo with a real-time behavioral AI engine designed to guide lifestyle choices. The company is conducting a five-year clinical trial (NCT05121844) to study weight and glycemic outcomes among platform users, with estimated enrollment of over 30,000 people without diabetes. While reimbursement remains limited, Signos positioned its $129-139/month subscription as a more accessible alternative to GLP-1 RAs. Signos’ FDA clearance highlights the momentum behind CGM as a key tool of lifestyle management, both in consumer wellness and adjunct to therapeutic care for those with diabetes.

10. Data interoperability comes into focus as diabetes data continues to be incorporated into routine clinical workflows

Diabetes data interoperability made progress in 2025 as EHR integrations and clinical workflows began to align more closely, although gaps remain. At DTM and ISPAD, presenters emphasized that data democratization now depends more on public application programming interfaces (APIs) and policy alignment across systems. While initiatives like iCoDE-2 and expanded EHR integrations are building the foundation for more equitable access to diabetes data, experts cautioned that fragmented regulation and lagging consent frameworks continue to cause barriers for clinical impact.

• Data standardization and EHR integration advanced meaningfully, establishing a foundation for more equitable and efficient use of diabetes data in clinical practice.
  • At DTM 2025, Dr. Juan Espinoza (Northwestern University) shared progress from the Integration of Connected Diabetes Device Data Into the Electronic Health Care #2 (iCoDE-2) initiative, which builds on iCoDE-1’s work with CGM to define a unified data model for insulin delivery across pumps, pens, and algorithms. The team developed an Insulin Dosing Profile (IDP) that presents 14 days of glucose metrics and insulin delivery data in a clinician-friendly EHR view. Dr. Espinoza plans to release the final iCoDE-2 report and a “public data dictionary” in 1Q26, which he described as a “living record” for insulin data standards that can be referenced by manufacturers and researchers.
    • In contrast, Dr. Pietro Randine (UiT The Arctic University of Norway) discussed the technical and ethical constraints of data access within Europe’s fragmented landscape. Device contracts and data infrastructures vary by country and often by region, forcing clinicians to manually transcribe device data into EHRs and creating more room for error. Limited public APIs, reliance on DIY data extraction tools that may violate terms of service, and costly third-party intermediaries further constrain real-time access, particularly for patients with low digital literacy.
  • At ISPAD, Mr. John Walsh (SweetSpot) highlighted that milestones such as Substitutable Medical Applications and Reusable Technologies (SMART) on Fast Healthcare Interoperability Resources (FHIR) and the FDA’s integrated CGM (iCGM) and alternate controller enabled (ACE) pump designations have fueled the development of diabetes technologies. However, he stressed that fundamental challenges remain, including the fact that data privacy and consent frameworks lag behind rapid advances in AI-driven decision support. Looking ahead, Mr. Walsh urged multidisciplinary collaboration to ensure interoperability is addressed as a priority as diabetes technology advances.
  • Several data integrations were launched into clinical practice in 2025, including EHR-centered workflows. In April, Abbott announced that LibreView accounts can now link directly to Epic, bringing FreeStyle Libre data into the EHR alongside Dexcom G7 and Glooko streams. In parallel, Glooko’s US integration with FreeStyle Libre extended its platform to ~4.5 million Libre users, now serving over 90% of the US CGM market, allowing patients and providers to interpret Libre data in the context of various health factors. Oura, maker of the Oura Ring, saw two notable integrations of its continuous health metrics with diabetes data: it launched app integration with Stelo in May, and partnered with Tidepool in November to build a real-world dataset integrating their wearable and diabetes device data, ultimately aiming to accelerate research on the physiological and behavioral factors that influence glycemic outcomes in diabetes management.

Top Ten Most Read Closer Look Reports in Therapy

1. Interview with Dexcom’s CEO Mr. Kevin Sayer on the launch of Stelo, T2D coverage, upcoming G8, and future of multi-analyte sensors – March 17, 2025 – Dynamic discussion explores product strategy and additional populations who could benefit from CGM
2. Interview with Glooko’s leadership team on its acquisition of Monarch Medical and the integration of inpatient insulin dosing algorithm EndoTool – November 11, 2025 – On the Monarch Medical acquisition, CGM integration and care transition, EndoTool’s role in primary care and population health management, raising integration awareness among HCPs, and upcoming eCQM reporting requirements
3. Dexcom announces FDA clearance of Dexcom G7 15 Day CGM for adults with diabetes – April 11, 2025 – Expected to launch in US in 2H25; Dexcom seeks to offer AID compatibility upon launch
4. Biolinq receives FDA De Novo Classification for Biolinq Shine as Glucose Range Monitoring System: autonomous, needle-free CGM – September 25, 2025 – Patch-based CGM designed to support metabolic health for people with T2D not on insulin
5. Interview with Biolinq CEO Mr. Rich Yang on Biolinq Shine, a patch-based CGM, and its FDA De Novo classification – November 14, 2025 – On FDA’s GRM category creation, Biolinq Shine’s indication, intradermal and semiconductor design with LED-screen dual display, access strategy, and multi-analyte platform roadmap
6. Medtronic 1Q25 (F4Q25) – May 21, 2025 – Diabetes division will separate as standalone company under Diabetes President and EVP Ms. Que Dallara; worldwide Diabetes revenue of $728 million (+10); MiniMed 780G FDA submissions for T2D and ultra rapid-acting insulins
7. Sequel announces US launch of twiist with Abbott’s FreeStyle Libre 3 Plus in 2Q25 – March 18, 2025 – The first FDA-cleared AID system with a Tidepool Loop-based algorithm will launch through the pharmacy channel for people with T1D aged six years and older
8. Dexcom to lay off 350 employees as company sharpens R&D focus – August 28, 2025 – Layoffs primarily affect operations and manufacturing at its San Diego headquarters; company reports R&D capital allocation as goal
9. Medtronic 4Q24 (F3Q25) – February 18, 2025 – Worldwide Diabetes revenue of $694 million (+8%; +10% operationally); Abbott-partnered CGM on track for FDA submission in 2H25; fifth consecutive quarter of double-digit Diabetes growth
10. Abbott 2Q25 – July 17, 2025 – Diabetes Care revenue totals nearly $2 billion (+20%; +19% operationally); discussions on pump integrations with upcoming dual glucose ketone sensor

Most Unexpected News/Biggest Surprises

Glucose Monitoring

1. Medtronic launches Instinct with MiniMed 780G in the US and extends rollout of Simplera Sync to additional European countries and the US
2. Abbott targets 2026 launch of dual glucose-ketone sensor, with five AID companies (Sequel, Tandem, Beta Bionics, Ypsomed and CamDiab, and Insulet) confirming planned integrations upon launch
3. Biolinq receives FDA De Novo Classification for Biolinq Shine as Glucose Range Monitoring System
4. Mr. Jake Leach to succeed Mr. Kevin Sayer as CEO effective January 1, 2026, after 21 years at Dexcom
5. Dexcom receives FDA clearance of Dexcom G7 15 Day CGM for adults with diabetes and launches the CGM on December 1
6. Dexcom to discontinue Dexcom G6 sensor effective July 1, 2026
7. Sequel Med Tech and Senseonics announce partnership to integrate Eversense 365 CGM with twiist
8. Dexcom receives FDA warning letter for manufacturing and quality control issues
9. Senseonics to take over commercialization of Eversense 365 from Ascensia
10. OTC CGM expansions: Abbott Lingo goes brick-and-mortar, Lingo and Dexcom Stelo join Amazon

Insulin Delivery

1. Medtronic announces MiniMed 780G CE-Mark for expanded use in T2D, pregnancy, and individuals aged 2+ years and FDA clearance for adults with T2D
2. FDA clears Tandem’s Control-IQ+ for adults with T2D
3. Diabetes division will separate as standalone company, MiniMed, under Diabetes President and EVP Ms. Que Dallara
4. Sequel begins full rollout of twiist in the US
5. Beta Bionics completes initial public offering
6. CMS finalizes competitive bidding rule for diabetes devices in the DME channel, bundling CGMs, insulin pumps, and supplies into a monthly rental payment
7. PK-PD glucagon “bridging” trial for Xeris’ glucagon for Beta Bionics’ bi-hormonal iLet validates safety and pharmacologic performance
8. More companies enter the patch pump game, with ongoing development work from Medtronic, Beta Bionics, and Tandem
9. Ypsomed Diabetes Care AG sold to TecMed as “mylife Diabetes Care AG”
10. FDA clears Tandem’s SteadiSet for up to seven days of use, with US launch slated for 2026
11. FDA accepts pediatric supplemental Biologics License Application for Afrezza, MannKind shares 52-week INHALE-1 data

Digital Health

1. Glooko acquires Monarch Medical, expanding connected diabetes platform with inpatient insulin dosing algorithms
2. Virta joins 60 healthcare technology organizations in CMS’s “Health Tech Ecosystem Initiative” aimed at making digital health tools user-friendly to patients and providers

Diabetes Therapy

Key Questions for 2026

Incretins

1. Might we see competitive challenges to the Novo Nordisk and Lilly duopoly on incretin therapies in 2026?
2. How will generic launches impact the pricing of branded incretin therapies, and will MFN pricing remain the standard globally?
3. How will the major GI side effects consistent across the class be addressed to reduce discontinuation rates?
4. How might patient segmentation come into play as oral incretins begin to receive approval?
5. How might we see increased uptake of incretin therapies in children as more data becomes available?
6. Will we see broader indications for these therapies in 2026, such as T1D or other complication reductions?

SGLT Inhibitors

1. How might dual-glucose-ketone monitoring affect the use of SGLT-2 inhibitors in people with T1D?
2. What additional safety protocols could the FDA require for Lexicon’s resubmission of Zynquista for T1D and CKD?
3. How might Medicare Drug Price Negotiation Program’s (MDPNP) negotiated price of Farxiga and Jardiance, which take effect on January 1, 2026, affect the systems cost? How might it affect out-of-pocket costs for patients?
4. Will lower costs of SGLT-2 inhibitors in MDPNP encourage the field to move toward earlier use of SGLT-2 inhibitors in a general population with T2D?

T1D

1. What lessons from the discontinuation of VX-264 will shape future encapsulation or immune-evasion strategies for stem cell-derived islet programs across the field?
2. Could immune invisibility (e.g. Sana Biotechnology’s hypoimmune gene-edited islets) interfere with normal, physiological clearance of dysfunctional β-cells, leading to long-term graft dysfunction?
3. How will regulators approach and evaluate risk for gene-edited hypoimmune cells, particularly with respect to longer-term oncogenic risk and the potential for off-target gene editing?

Complications

1. What clinical education is required meaningfully shift away from opioids toward newer mechanisms, like NaV1.8 inhibitors?
2. What patient subgroups (severity, duration of DPN, and comorbidities) will derive the greatest benefit from Lexicon’s pilavapadin?
3. Could limb outcomes become a required endpoint in future CVOTs for therapies in obesity and metabolic disease?
4. How will regulators and payers value functional endpoints (e.g. walking distance) versus hard limb events?

Insulin

1. With the resubmission of its BLA, will Novo Nordisk’s Awiqli receive approval in the US in 2026?
2. How will the approval of Sanofi’s Merilog, as the first rapid‑acting biosimilar to NovoLog, impact Novo Nordisk’s sales?
3. How might the cap on insulin at $35/month for all patients in the US, effective January 2026, improve patient compliance, and what metrics might be used to measure this?
4. Might we see approval of IcoSema in the EU in 2026?
5. How will the increasing uptake of incretin therapy impact insulin use?

What’s Coming in 2026?

Incretins and weight loss

Altimmune

1. Phase 3 trial evaluating pemvidutide (dual GLP-1/glucagon RA) for MASH with F2 or F3 fibrosis is expected in 2026, following the phase 2b IMPACT trial (n=212) and an end-of-phase 2 meeting with the FDA in 4Q25.

AZ

1. Data for phase 2b VISTA (n=304) and SOLSTICE trials (n=406) evaluating AZD5004 (oral GLP-1 RA) for obesity or overweight are expected in 1H26. The therapy is expected to enter phase 3 trials pending this data.
2. Data from phase 2b APRICUS (n=262) and phase 2 ARAY trials (n=64) evaluating AZD6234 (long-acting amylin analog) for obesity are expected in 1H26.
3. Results for phase 2b ASCEND trial (n=360) of AZD9550 (dual GLP-1/glucagon RA) in combination with AZD6234 for adults with obesity or overweight with at least one weight-related comorbidity are expected in 2H26.

Lexicon

1. IND filing for LX9851 (oral ACSL5 inhibitor) in obesity expected by the end of 2025 under its license agreement with Novo Nordisk.

Lilly

1. Filing for the MACE indication of tirzepatide is expected by the end of 2025, based on full results from the SURPASS-CVOT.
2. Initiation of global regulatory filings of orforglipron for the obesity indication, upon the completion of the ATTAIN-2 trial, and the launch pending approval is expected in 2026.
3. Up to six phase 3 results for retatrutide (triple GLP-1/GIP/glucagon RA) will be available by 2026.
4. Lilly has agreed to the Most-Favored-Nation Pricing to offer tirzepatide and orforglipron at discounted prices. 

Merck

1. Efinopegdutide (GLP-1/glucagon receptor co-agonist MK-6024) continues to be evaluated in phase 2b (n=360) for MASH, with completion expected by the end of 2025.

Novo Nordisk

1. Novo Nordisk expects a regulatory decision for semaglutide 7.2 mg in early 2026 and approval of semaglutide 7.2 mg in a single-dose pen in 2H26.
2. Novo Nordisk has agreed to the “maximum fair prices” (MFPs) set by the US Inflation Reduction Act for three of its semaglutide medicines – Ozempic, Rybelsus, and Wegovy – which will take effect under Medicare Part D in 2027.
3. Novo Nordisk has agreed to the Most-Favored-Nation Pricing to offer semaglutide at discounted prices.
4. Novo Nordisk plans to initiate a phase 3 program for once-weekly subcutaneous and once-daily oral amycretin for people with T2D in 2026 to evaluate amycretin in adults with T2D.
5. Phase 3 trial evaluating CagriSema in children with obesity or who are overweight is set to begin in January 2026 and is estimated to complete in September 2033.

Regeneron

1. Phase 2 study of once-daily oral GIPR antagonist, PF-07976016, expected December 2025.

Roche

1. Phase 3 trials of CT-388 (once-weekly dual GLP-1/GIP RA) for obesity with (n=360) or without T2D (n=450) is expected to initiate in 1H26.
2. A phase 2 trial (n=340) of CT-996 (once-daily oral GLP-1 RA) is expected to complete in July 2026.

Viking

1. IND filing for dual amylin and calcitonin receptor agonist (DARCA) is planned for 1Q26.
2. Phase 3 VANQUISH-1 (n=4,500) and VANQUISH-2 (n=1,100) trials for subcutaneous VK2735 (dual GLP-1/GIP RA) in obesity and T2D are expected to be completed in mid 2027.

Zealand

1. A phase 2 trial for a fixed-dose combination of petrelintide and Roche’s dual GLP-1/GIP RA, CT-388, is on track to initiate in 1H26.
2. Topline results of the phase 3 SYNCRHONIZE-1 (n=727) and SYNCHRONIZE-2 trials (n=756) of BI/Zealand’s survodutide (dual glucagon/GLP-1 RA) for people with overweight or obesity without or with T2D, respectively, are expected in 1H26. The trials are expected to complete in February and April 2026.
3. SYNCHRONIZE-CN trial (n=307) evaluating survodutide in people with obesity in China is expected to complete in 1Q26.

SGLT Inhibitors

AstraZeneca

1. Farxiga is being investigated as a combination therapy with baxdrostat (highly selective aldosterone synthase inhibitor), balcinrenone (nonsteroidal mineralocorticoid receptor modulator), and zibotentan (endothelin A receptor blocker) in phase 3 trials.
2. Medicare Drug Price Negotiation Program’s negotiated price of Farxiga $178.50 for a monthly supply, down 68% from $556 Farxiga, will take effect on January 1, 2026.

BI/Lilly

1. Medicare Drug Price Negotiation Program’s negotiated price of Jardiance, down 66% from $573 to $197, will take effect on January 1, 2026.

T1D

Advant Technologies + SGAustria

1. Preclinical development of encapsulated stem cell-based therapies for T1D and insulin-dependent T2D is expected to continue in 2026.

Century Therapeutics

1. IND-enabling studies for CNTY-813 are expected to complete by year-end (2025), with a regulatory IND submission targeted for 2026.

Sana Biotechnology

1. Advancement of the hypoimmune pancreatic islet (HIP) platform into its SC451 program. Clinical follow-up is expected to continue in 2026 following first-in-human proof-of-concept data generated in 2025.

Eldeon Pharmaceuticals

1. Ongoing clinical evaluation of tegoprubart in people with T1D undergoing islet transplantation is expected to continue in 2026 following encouraging early insulin-independence data.

Pluristyx

1. Pluristyx will continue preclinical development of its immune-cloaked, safety switch-enabled iPSC line for T1D through its collaboration with Breakthrough T1D in 2026.

Vertex

1. Regulatory submission for zimislecel (VX-880) is planned for 2026 following completion of enrollment in the phase 1/2/3 FORWARD study (n=52) and ongoing manufacturing analyses.
   1. Dosing in the phase 3 portion of the study is ongoing.

Sernova

1. The last cohort in Sernova’s phase 1/2 trial evaluating the Cell Pouch system in people with T1D is expected to initiate by the end of 2025, with clinical data expected in 2026.

Insulin

Lilly

1. With regulatory submission of once-weekly insulin efsitora alfa for T2D in 3Q25, FDA decision may be shared next year.

Novo Nordisk

1. FDA decision for Awiqli (once-weekly insulin icodec) in T2D may be shared next year, given that Novo Nordisk resubmitted the application in September 2025.
2. Fiasp and NovoLog were selected for the first cycle of the US Medicare Drug Price Negotiation Program (MDPNP), with discounted prices (down 75% to $199/month), which will take effect on January 1, 2026.

Complications

Vertex

1. Commercial launch and market expansion of Journavx (suzetrigine) are expected to continue in 2026 following FDA approval in 2025.

Lexicon

1. Initiation of phase 3 trials for pilavapadin (LX9211) in diabetic neuropathic pain (DPN) is planned for 2026, following an end-of-phase 2 feedback meeting (expected early next year).

Novo Nordisk

1. Additional analyses of SOUL, FLOW, and STRIDE trial data for rybelsus (semaglutide) supporting reduced major adverse limb events with oral semaglutide are expected to continue in 2026.

Bayer

1. The phase 3 REDEFINE-HF trial (n=5,200) evaluating finerenone in patients with acute decompensated HF and HFmrEF/HFpEF is expected to complete in April 2026.
2. The phase 3 CONFIRMATION-HF trial (n=1,500) assessing finerenone in combination with SGLT-2 inhibitors in hospitalized HF patients is expected to complete in August 2026.
3. The phase 3 FIND-CKD trial (n=1584) evaluating finerenone in people with CKD without diabetes is estimated to complete in February 2026.

Lupin

1. Lupin holds FDA tentative approvals for generic dapagliflozin and generic canagliflozin, positioning the company to launch these products as patent and exclusivity barriers lift.

Themes

1. Incretin-based therapies: New indications and outcomes trial in the heart, kidneys, liver, and limbs

In 2025, incretin therapies continued to dominate headlines, reshape treatment protocols, and expand into new indications. The year was marked by both regulatory successes and increased accessibility, particularly given expanding indications for a class of medication that has taken the obesity landscape by storm.

• This year, incretin therapies continued to demonstrate benefits beyond glycemic health. Novo Nordisk’s Ozempic (semaglutide) secured new approvals across three major indications. In the US and Canada, semaglutide was approved for risk reduction in kidney disease progression, kidney failure, and cardiovascular death in adults with T2D and CKD. The approval was based on the phase 3 FLOW trial (n=3,533), which showed a 24% reduction in primary kidney disease events. In June 2025, Ozempic was granted an expanded label in the EU based on the phase 3b STRIDE trial (n=792), which demonstrated a 21% improvement in walking distance and a 54% reduction in the composite of rescue therapy, major adverse limb events, or mortality. In August 2025, Novo Nordisk’s Wegovy (semaglutide) was approved in the US for MASH in adults with moderate to advanced fibrosis based on Part 1 of the phase 3 ESSENCE trial (n=1,200), which showed 63% resolution of steatohepatitis without worsening fibrosis and 37% improvement in fibrosis without worsening steatohepatitis, compared to 34% and 23% with placebo, respectively.
  • While not approved yet for CV risk reduction, Lilly’s Mounjaro (tirzepatide) delivered compelling results in the landmark phase 3 SURPASS-CVOT (n=13,299). In this head-to-head comparison with dulaglutide, tirzepatide conferred a significant 16% reduction in all-cause mortality, nonsignificant 12% weight loss (vs. 5%), and a significant 1.7 percentage point A1c reduction (vs. 0.9 percentage point). In people with CKD, tirzepatide slowed eGFR decline by 3.54 mL/min/1.73 m² compared to dulaglutide, further supporting its potential as a cardiorenal and metabolic therapy.
• On the access front, the expiration of liraglutide patents in major markets catalyzed a wave of generic launches. Teva, Lupin, Biocon, and Meitheal all entered the market with liraglutide generics, some priced up to 70% lower than branded versions. Moreover, in Canada, semaglutide is set to become generic in January 2026 following a patent lapse due to non-payment. Sandoz and Apotex plan to launch generic semaglutide in 2026. Likewise, Hims&Hers announced plans to enter the Canadian market with discounted generic semaglutide following the termination of its partnership with Novo Nordisk to sell discounted cash-price Wegovy in the US. These developments reflect growing momentum toward lower-cost incretin therapies across geographies and distribution models. We’re watching closely how these generics may impact pricing and access. In addition to generic launches, the US government has reached agreements with Lilly and Novo Nordisk to lower the cost of GLP-1 RAs.Read more about the Most-Favored-Nation (MFN) pricing negotiations and the Centers for Medicare and Medicaid Services’ (CMS) Medicare Drug Price Negotiation Program (MDPNP) in the big picture theme.

2. Expanding competitive landscape for oral GLP-1 RAs and multi-incretins for T2D

2025 marked a dynamic year for oral incretin therapies, with major phase 3 readouts, regulatory approvals, and program discontinuations. We are encouraged by the continued advancement of oral incretins as they can expand access, simplify manufacturing, and reduce treatment burdens.

• For cardiovascular protection, Novo Nordisk’s Rybelsus (oral semaglutide) was approved in both the US and EU for reducing major adverse cardiovascular events (MACE) in adults with T2D and high cardiovascular risk. These approvals were based on the phase 3b SOUL trial (n=9,650), which demonstrated a 14% reduction in MACE compared to placebo.
• Lilly’s orforglipron (oral GLP-1 RA) demonstrated superiority to multiple comparators across three phase 3 trials in people with T2D. In ACHIEVE-2 (n=888), orforglipron (36 mg) reduced A1c by 1.7 percentage points vs. 0.8% with dapagliflozin in people with T2D and inadequate glycemic control on metformin. In ACHIEVE-5 (n=520), orforglipron reduced A1c by up to 2.1 percentage points vs. 0.8 percentage point with placebo in people with inadequately managed T2D on insulin glargine. In ACHIEVE-3 (n=1,698), orforglipron conferred 9.2% weight loss vs. 5.3% with oral semaglutide, and 37.1% of participants on the highest dose achieved A1c <5.7%, compared to 12.5% in the oral semaglutide group. Moreover, in the ATTAIN-2 trial (n=1,500) presented at ObesityWeek 2025, orforglipron conferred up to 11% weight loss vs. 2% with placebo and 1.8 percentage point reduction in A1c vs. 0.1 percentage point with placebo in adults with overweight or obesity and T2D. Notably, 75% of participants on the highest dose achieved an A1c ≤6.5%, reinforcing orforglipron’s potential as a foundational therapy for diabetes.
• While we were excited about the therapeutic potential of Pfizer’s danuglipron (oral GLP-1 RA), the company discontinued development of this program in April 2025. The decision followed a case of potential drug-induced liver injury and high rates of GI-related adverse events in earlier trials. As background, in a phase 2b trial (n=628), twice-daily danuglipron conferred up to 13% weight loss, but discontinuation rates exceeded 50% across all doses. Nonetheless, we are excited for the continued development in oral incretin therapies, including AstraZeneca’s oral GLP-1 RA AZD 5004 and Viking’s oral VK2735 (dual GLP-1/GIP RA) in phase 2.
• Dual incretins continued to gain momentum, with Innovent’s dual GLP-1/glucagon RA mazdutide receiving approval from China’s regulatory agency for glycemic management in T2D based on the phase 3 DREAMS-1 (n=320) and DREAMS-2 (n=731) results. More recently, mazdutide 9 mg conferred a 19% weight loss in the GLORY-2 trial (n=462), with nearly half of participants achieving ≥20% weight loss. Based on the results, China’s National Medical Products Administration (NMPA) accepted Innovent’s supplementary application for the 9 mg dose. Meanwhile, Novo Nordisk’s CagriSema (fixed-dose cagrilintide + semaglutide) conferred a 13.7% weight loss in people with overweight or obesity, compared with 3.4% with placebo, in the phase 3 REDEFINE-2 trial (n=1,206). 

3. Toward the holy grail: Advances in cell replacement therapies for T1D

Therapeutic landscape for cell replacement therapies for T1D continued to evolve in 2025, with progress spanning stem cell-derived islets, hypoimmune platforms, and immunosuppressants. Vertex remained a central leader in the cell therapy space with its zimislecel program in the phase 1/2/3 trial, while Sana Biotechnology, Adocia, and others advanced early clinical- and preclinical-stage candidates.

• Vertex offered substantial updates across its T1D cell therapy programs this year. Zimislecel (VX-880), a stem cell-derived islet with standard immunosuppression, continues to be evaluated in the pivotal phase 1/2/3 FORWARD study (n=52), which completed enrollment in 3Q25. Vertex has postponed dosing completion in the phase 3 portion of the study to conduct an “internal manufacturing analysis,” but regulatory submission remains planned for 2026.
  • At ADA 2025, Vertex presented one-year follow-up data from the FORWARD phase 1/2 study, following interim data presented at EASD 2024. Of the 12 participants who received full dose therapy, none experienced severe hypoglycemic events between Days 90 and 365, and all achieved an A1c of <7% or a ≥1% reduction from baseline, meeting the primary endpoint. Moreover, 10 of 12 achieved insulin independence. The remaining two had 70% and 36% reductions in daily insulin requirements.
  • Separately, in March 2025, Vertex discontinued VX-264, a stem cell-derived islets encapsulated in an immune-evasive device, after Parts A and B of the phase 1/2 study (n=17) failed to demonstrate clinically meaningful increase in C-peptide. Based on the data, Vertex decided not to launch the Part C of the trial.
• Also in cell therapy, at ADA 2025, Sana Biotechnology presented six-month results from the first human transplant of gene-edited hypoimmune pancreatic islet (HIP) cells in a person with longstanding T1D. As background, HIP cells incorporate HLA-I/II knockout and CD47 overexpression to evade immune detection without immunosuppression. The trial demonstrated rapid C-peptide restoration by Week 4 and sustained responses through Week 26. MRI and PET-MRI confirmed viable grafts with no inflammation, and no safety concerns were reported. Sana Biotechnology will incorporate the HIP platform into SC451, a stem cell-derived islet therapy in development as a one-time treatment for T1D without insulin or immunosuppression.
• Beyond Vertex and Sana, early-stage cell therapy efforts are broadening.
  • On encapsulation and scaffolding, Adocia reported encouraging in vivo results for AdoShell, its immune-evasive scaffold for stem cell-derived islets, at ADA 2025. In preclinical models, islets encapsulated with AdoShell showed an increase in human C-peptide secretion over three months and a three-fold increase in insulin secretion after explant. In vitro, encapsulated islets retained viability, functionality, and insulin secretion comparable to non-encapsulated islets. Adocia originally announced plans for a first-in-human submission by 2H25, but recent updates have extended this goal to 3Q26.
  • Seattle-based Pluristyx and Breakthrough T1D announced a collaboration to develop an “immune-cloaked” and “safety switch-enabled” induced pluripotent stem cell (iPSC) line that would not require chronic immunosuppression.
  • Philadelphia-based Century Therapeutics launched CNTY-813, an iPSC-derived ß-cell islet program, using the company’s Allo-Evasion 5.0 technology. Preclinical data conferred rapid, sustained glucose normalization and glucose-responsive insulin secretion with CNTY-813 therapy. IND-enabling studies are planned by year-end with an IND targeted for 2026.
  • Las Vegas-based Avant Technologies and Singapore-based SGAustria announced a joint venture to develop encapsulated stem cell-based therapies for T1D and insulin-dependent T2D, combining Avant’s expertise in cell-line engineering and SGAustria’s in encapsulation technology.
  • On immunosuppression, Eledon Pharmaceuticals is developing tegoprubart, an anti-CD40L antibody, as a less toxic immunosuppressive therapy for people with T1D who undergo islet transplantation. Early data showed insulin independence in all six subjects three to 12 months post-treatment, with A1c values ranging from 4.7% to 6.0%.
  • Finally, funding for T1D programs continued to expand. In October 2025, Breakthrough T1D’s venture arm, the T1D Fund, launched a $150 million fundraising campaign to bolster its investment capacity and accelerate high-potential therapies. The campaign has already secured $60 million toward its goal.

4. Momentum continues for disease-modifying therapies in T1D

In 2025, disease-modifying therapies advanced significantly, led by new updates on Sanofi’s Tzield (teplizumab). Following FDA approval in November 2022 for people with stage 2 T1D, Sanofi secured approvals in other countries, including Canada, China, and the UK. Most recently, in November 2025, Sanofi received a positive CHMP opinion recommending EU approval of teplizumab (Teizeild) for stage 2 T1D. In the US, teplizumab received the FDA’s new Commissioner’s National Priority Voucher for a potential indication of preserving beta cell function in people with recent onset stage 3 T1D. With the expedited review process, the regulatory decision is now expected in 1H26. The application for stage 3 T1D is based on the PROTECT (n=328) trial, in which Tzield demonstrated beta-cell function preservation in children and adolescents with recent onset T1D. A post hoc analysis of this study, presented at ATTD 2025, further found that teplizumab conferred meaningful improvements in TIR (+1.6 hours/day), lowered hyperglycemia incidence, and decreased insulin use compared to placebo.

• In the pipeline, companies continued to invest in novel mechanisms.SAB Biotherapeutics raised $175 million to support the phase 2b SAFEGUARD trial (n=142) of SAB-142, a human anti-thymocyte immunoglobulin (hIgG), following positive phase 1 results. Cambridge, MA-based Zag Bio launched with $80 million in financing to advance ZAG-101, a bifunctional antibody designed to induce central immune tolerance by presenting beta-cell antigens to the thymus. Chicago-based COUR Pharma began dosing in its phase 1b/2a trial of CNP-103 (n=72), a tolerogenic nanoparticle therapy for stages 1, 2, and 3 T1D.
• Existing treatments, like verapamil (for angina pectoris and cardiac arrhythmias) and baricitinib (indicated for autoimmune diseases like rheumatoid arthritis), are also evaluated for potential benefits on C-peptide preservation. As presented at EASD 2025, the phase 2 MELD-ATG trial (n=117) confirmed that low-dose ATG (0.5 mg/kg) significantly preserved C-peptide in young people with new-onset T1D, establishing a minimum effective dose with improved tolerability. The Ver-A-T1D trial (n=136) of verapamil did not meet its primary endpoint, though C-peptide remained higher with treatment. Two-year outcomes from the BANDIT trial (n=91) showed that baricitinib significantly preserved C-peptide during the treatment phase but not beyond, with similar patterns observed for insulin requirements.

5. Meeting the unmet needs in T1D: Finerenone, GLP-1 RAs, and SGLT inhibitors as adjunctive therapies to insulin

In 2025, the field continued to push for adjunctive therapies in T1D to reduce the burden of cardiovascular (CV) and renal complications. As we heard at ADA 2025, people with T1D – including those with well-managed diabetes – face a two- to four-fold increased risk for CV disease compared to those without T1D. Yet, insulin remains the only approved therapy, with adjunctive medications limited to amylin analog Symlin (pramlintide) approved in 2004. To address this therapeutic gap, nonsteroidal mineralocorticoid receptor antagonist (nsMRA) finerenone, GLP-1 RAs, and SGLT inhibitors have been evaluated as add-on therapies to insulin.

• In the landmark phase 3 FINE-ONE trial (n=241), finerenone significantly reduced uACR (urine albumin-to-creatinine ratio) by 25% in people with T1D and chronic kidney disease (CKD) at six months. This benefit was consistent across all prespecified subgroups, including age and sex. On safety, treatment-emergent adverse event rates were comparable between treatment and control groups. Consistent with previous trials, finerenone led to higher rates of hyperkalemia (high blood potassium level; 10%; n=12) than placebo (3%; n=4), but its clinical impact was limited. In Bayer’s 3Q25 call, management commented that finerenone is the first therapy in 30 years to demonstrate positive results in addressing CKD in this population. Given that ~27% of people with T1D have CKD, we are encouraged that an effective and safe medication may soon become available for this population. As background, Kerendia (finerenone) was approved for CKD in people with T2D in 2021 and heart failure with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF) in July 2025.
• In the phase 2 TIRTLE1 trial (n=24), tirzepatide reduced body weight by 9% and insulin dose by 33% in adults with T1D and obesity (BMI ≥30 kg/m²) at Week 12. Tirzepatide also reduced A1c by 0.5 percentage point from a baseline of 7.3% (vs. 0.2 percentage point with placebo; p=0.05), and numerically improved Time in Range (TIR) and Time below Range (TBR, p=0.17). Notably, tirzepatide led to a 25% reduction in basal insulin dose (p=0.002) and 49% reduction in bolus insulin dose (p=0.008), compared to placebo. Given the positive results, Lilly launched a phase 3 trial (n=905) for people with T1D and obesity, with completion expected May 2027. Separately, Roche also announced in 3Q25 that it will advance CT-868 (once-daily dual GLP-1/GIP RA) to phase 3 for people with T1D and BMI ≥25 kg/m². The decision is based on the recently completed 16-week phase 2 trial (n=111), the results of which are expected in 2026. The phase 3 trial is expected to launch in 2026. We are encouraged by these advancements, especially given that two-thirds of adults with T1D live with overweight or obesity, and insulin therapy is linked to increased risk of weight gain.
• SGLT inhibitors continue to be considered for use in T1D. Although off-label SGLT-2 inhibitor use in people with T1D has increased from 0.1% in 2010 to 2.4% in 2023 for its known cardiorenal protection, its use is also associated with 3.2x greater diabetic ketoacidosis (DKA) risk in people with T1D. Despite the increased risk, most people with diabetes do not regularly test ketones: urine testing remains common, though less reliable, than blood measurement, and many rely on persistent, CGM-detected hyperglycemia alone to trigger ketone checks. Furthermore, an alarming proportion of patients with diabetes remain unaware of DKA symptoms and are unprepared for emergencies consistent with guidelines. Technological advancements toward dual glucose ketone (DGK) monitoring offer promise for safer SGLT inhibitor use in people with T1D. At EASD 2025, Dr. Richard Bergenstal (International Diabetes Center) said that DGK monitoring has could reduce DKA by providing real-time ketone data, integrating alerts, and supporting early intervention.
  • On pharmacologic advancements, Lexicon submitted additional clinical data to the FDA in September 2025, which would support plans to resubmit the New Drug Application (NDA) for Zynquista (sotagliflozin), an oral dual SGLT-1/SGLT-2 inhibitor, for T1D and CKD. New data includes results from three ongoing trials designed to offer more insights into DKA rates, mitigation strategies, and renal outcomes. Lexicon expects feedback from the FDA in 4Q25. As background, in November 2024, Lexicon received a “deficiencies preclude discussion letter” from the FDA regarding the company’s NDA resubmitted in July 2024 for Zynquista. This letter followed an 11:3 vote against Zynquista’s benefit-to-risk profile at the EMDAC meeting in October 2024, which noted insufficient evidence that Zynquista’s benefits of A1c reduction outweighed the risk of DKA.

6. Once‑weekly insulin moves closer to market with robust phase 3 data

This year marked significant progress in insulin therapy with updates in innovation, biosimilars, and affordability. Once‑weekly insulin advanced meaningfully, with Novo Nordisk resubmitting its Biologics License Application (BLA) to the FDA for Awiqli (icodec) in T2D in September 2025, following a Complete Response Letter (CRL) issued in July 2024 that requested additional information on manufacturing processes and T1D indication. Novo Nordisk did not pursue a T1D indication in its resubmission due to increased rates of hypoglycemia. Awiqli has already been approved in the EU, Japan, and China. Across six trials in the phase 3 ONWARDS program, Awiqli demonstrated noninferior A1c reductions compared to insulin glargine or insulin degludec, with favorable safety profile in T2D. Meanwhile, Lilly advanced its once-weekly insulin efsitora alfa through the phase 3 QWINT program, announcing full results of QWINT-1, 3, and 4 at ADA 2025. Efsitora alfa demonstrated non-inferior A1c reduction compared to insulin glargine and insulin degludec in people with T2D on different insulin requirements (initiating basal insulin, already on basal insulin, and basal-bolus insulin, respectively). Results from the QWINT- 2 and 5 trials announced EASD 2024 similarly found non-inferior A1c reduction compared to insulin degludec in people with insulin-naïve T2D and T1D, respectively. However, in people with T1D, insulin efsitora alfa caused higher rates of hypoglycemia. In 3Q25, Lilly submitted for regulatory approval for T2D in the US. These candidates have the potential to reduce injection burden and expand adoption in primary care.

• On combination therapy, IcoSema (once-weekly icodec + semaglutide) demonstrated non‑inferior glycemic control, superior weight loss, and fewer hypoglycemic events compared to basal‑bolus therapy in the phase 3a COMBINE‑3 trial (n=679). Importantly, patient satisfaction scores were higher, compared to those on basal-bolus therapy.
• Ultra‑rapid insulin innovation continued with Adocia and Tonghua Dongbao’s BioChaperone Lispro, which met its primary endpoint of non‑inferiority in A1c reduction when compared with Humalog in a phase 3 trial (n=1,040) in China. The candidate also reduced postprandial glucose excursions and improved daily mean glucose, with comparable safety.
• Alternative forms of insulin, including inhaled and oral insulin, also gained new momentum. MannKind’s Afrezza received FDA acceptance for a pediatric indication. The supplemental Biologics License Application (sBLA) was supported by the phase 3 INHALE‑1 trial (n=230) results, where Afrezza, in combination with basal insulin, showed comparable efficacy and safety to MDI in youth with T1D and T2D. The PDUFA is set for May 2026, and has the potential to expand insulin options for children and adolescents if approved. Meanwhile, in October 2025, Oramed launched a US‑based trial of ORMD‑0801 (oral insulin) in people with T2D, focusing on the high-responder subgroup identified from Oramed’s previous phase 3 trial (n=346).

On the biosimilar and accessibility front, several rapid‑acting biosimilars were approved this year. In February 2025, Sanofi’s Merilog (insulin aspart-szjj) became the first FDA‑approved rapid‑acting biosimilar to NovoLog. In July 2025, Biocon’s Kirsty (insulin aspart-xjhz) was approved as the first and only interchangeable biosimilar to NovoLog. This momentum follows previous years, when Semglee (glargine‑yfgn) and Rezvoglar (glargine‑aglr) were approved as interchangeable biosimilars for Lantus (basal insulin glargine). We are hopeful that these approvals of biosimilar products may promote greater competition in the insulin market and expand access for patients.

• The insulin market also reached several affordability milestones this year. In September 2025, Sanofi expanded its Valyou Savings Program to cap all insulins at $35/month for all patients, regardless of insurance status, starting January 2026. Moreover, in October 2025, Biocon partnered with Utah-based nonprofit Civica Rx and California’s CalRx initiative to launch insulin glargine‑yfgn in the US at $45 for a box of five pens nationwide. Under CalRx, California residents will pay just $11 per pen.

7. SGLT-2 inhibitors and finerenone as foundational therapies for T2D and comorbidities; new cohorts of interest expanding potential indications

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (nsMRA), formerly approved for CKD in T2D under the brand name Kerendia, had a landmark year with major regulatory and clinical developments. In July 2025, the FDA expanded Kerendia’s indication to include heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF), following a Priority Review Designation issued in March. The decision was supported by the phase 3 FINEARTS-HF trial (n=6,001), in which finerenone demonstrated a 16% risk reduction in the composite endpoint of total heart failure (HF) events and cardiovascular death over 2.5 years.

• Momentum for finerenone in heart failure is progressing through Bayer’s MOONRAKER program (n>15,000), which features three ongoing phase 3 trials across the HF spectrum:
  • The phase 3 REDEFINE-HF trial (n=5,200) is investigating finerenone for patients with acute decompensated HF and HFmrEF/HFpEF, and is expected to complete in April 2026.
  • The phase 3 CONFIRMATION-HF trial (n=1,500) is assessing a combination therapy of finerenone and SGLT-2 inhibitors in patients hospitalized with HF. The trial is expected to complete in August 2026.
  • The phase 3 FINALITY-HF trial (n=2,600) is studying finerenone in patients with HFrEF who are unable to tolerate steroidal MRAs. The trial is expected conclude in April 2028.
• Beyond HF, finerenone is evaluated in various understudied populations, including: (i) people using SGLT-2 inhibitors; (ii) children; (iii) people with T1D; and (iv) people without diabetes. In the phase 2 CONFIDENCE trial (n=800), simultaneous initiation of GLP-1 RAs and SGLT-2 inhibitors was associated with ~30% greater reduction in uACR than either therapy in isolation in T2D and CKD. The results demonstrate the early and additive benefits of finerenone in kidney health and support combination therapy for maximal risk reduction, as included in the new ADA Standards of Care 2026.
  • Another landmark study was the phase 3 FINE-ONE trial (n=220), which found that finerenone significantly reduced uACR by 25% at six months in people with T1D and CKD. The potential impact of this study is great, as people with T1D and CKD have been limited to intensive glycemic management and RAAS inhibitors for over three decades.
  • Other ongoing studies of finerenone include: (i) the phase 3 FIND-CKD trial (n=1,584) investigating finerenone in people with CKD without diabetes; (ii) the phase 3 FIONA trial (n=219) evaluating finerenone and an ACEi/ARB in children with CKD and proteinuria; and (iii) the phase 3 FIONA OLE trial (n=100), which is an 18-month open-label extension study of FIONA.

SGLT-2 inhibitors continue to be central to the management of T2D, CKD, and heart failure. Over the years, ADA and KDIGO guidelines have increasingly positioned SGLT-2 inhibitors as a first-line therapy. For example, the ADA Standards of Care 2026 recommends early SGLT-2 inhibitor use in people with T2D and HF or CKD. In the UK, the NICE draft guidance recommends SGLT-2 inhibitors as a first-line therapy with or without metformin for the general population with T2D; this change would save nearly 22,000 lives if 90% of the patient population takes the dual therapy. Despite abundant evidence and guidelines, real-world uptake of SGLT-2 inhibitor remains low, underscoring the importance of greater access and accessibility.

• SGLT-2 inhibitors will begin to go generic over the next few years. AZ’s Farxiga (dapagliflozin) lost exclusivity for its glycemic management indication in people with T2D in October, although its method-of-use patents related to CKD extend to 2029. Jardiance’s compound patent will expire in 2029 in the US and Europe and 2030 in Japan. Merck’s Steglatro (ertugliflozin) patents will expire in 2030 in the US and 2029 in the EU, China, and Japan. The FDA tentatively approved generic versions of two SGLT-2 inhibitors developed by Mumbai-based Lupin, dapagliflozin and canagliflozin, in November 2023. Lupin is expected to launch both in as patent protections lift.
• In the US, the new Medicaid prices of AstraZeneca’s Farxiga and BI/Lilly’s Jardiance will take effect in January 2026. As background, the Centers for Medicare and Medicaid Services (CMS) had announced in 2024 the negotiated prices – referred to as “Maximum Fair Prices” – for the first 10 drugs included in the Medicare Drug Price Negotiation Program (MDPNP). Farxiga’s negotiated price would be $179, down 68% from the list price of $556, while Jardiance’s negotiated price would be $197, down 66% from $573. While list prices do not reflect out-of-pocket costs for Part D beneficiaries, we imagine the new change will certainly lower the systems cost.
• Cheaper SGLT-2 inhibitor TheracosBio’s Brenzavvy (bexagliflozin) has also become available this year. In June 2025, TheracosBio partnered with Mark Cuban’s Cost Plus Drug Company and Publix pharmacies to offer Brenzavvy at ~$50/month. In October 2025, TheracosBio and Wellgistics Health announced a partnership to offer Brenzavvy at over than 6,500 independent and chain pharmacies nationwide at a lower cost.

8. MASH has a giant year, with semaglutide becoming the second approved option for the treatment in the US; liver health becomes the next frontier for cardiometabolic development

In August 2025, Wegovy (semaglutide 2.4 mg) became the second therapy approved by the US FDA for the treatment of MASH in adults with moderate to advanced liver fibrosis (stages F2 to F3 fibrosis). The approval was based on Part 1 of the phase 3 ESSENCE trial (n=1,200), in which Wegovy conferred a statistically significant and superior improvement in liver fibrosis, as well as resolution of steatohepatitis with no worsening of liver fibrosis compared to placebo. The approval of Wegovy follows the approval of Madrigal’s Rezdiffra (resmetirom), which was the first FDA-approved treatment for this population in March 2024. Beyond these two approved therapies, 2025 brought high interest in liver health as a whole. Mergers and acquisitions became contentious at times as pharmaceutical giants Novo Nordisk, Roche, and Pfizer fought for a stake in the expanding liver health market through candidates such as FGF21 analog efruxifermin.

• Madrigal’s resmetirom expanded its reach in 2025 and addressed the potential competition that Wegovy offers to Rezdiffra.
  • In August 2025, the European Commission approved Rezdiffra (resmetirom) for use in MASH with moderate to advanced liver fibrosis. The decision followed Rezdiffra receiving a positive recommendation by the European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in June 2025. Madrigal plans to begin the European rollout of the therapy in Germany and expand on a country-by-country basis.
  • In Madrigal’s 3Q25 earnings call, Rezdiffra’s tolerability and adherence were emphasized, with an estimated 80% patient adherence or higher. In comparison, discontinuation rates for GLP-1 RAs have often approached 70% among patients with obesity. Wegovy also targets a broader range of liver fibrosis for treatment, including F1 fibrosis and the prevention of MASH, while Rezdiffra treats F2 and F3 (moderate-advanced) fibrosis. Madrigal therefore believes that Wegovy is not a direct competitor for Rezdiffra. As prescriptions for the two therapies continue to expand in 2026, we will follow updates on this dynamic.
• Large pharmaceutical companies completed high-value acquisitions related to liver health in 2025, signaling their confidence in the future of this therapeutic class, including Roche’s acquisition of 89bio (FGF21 analog pegozafermin in phase 3), Novo Nordisk’s of Akero Therapeutics (FGF21 efruxifermin in phase 3), and Pfizer’s of Metsera (several early-stage GLP-1 RAs and amylin candidates). Read more on this in this big picture theme on M&A!
• Beyond leading MASH therapies resmetirom and semaglutide, the treatment landscape further expanded in 2025 with non-incretin and incretin-based therapies.
  • In June 2025, Rivus Pharmaceuticals announced positive topline results from its phase 2 M-ACCEL trial (n=219) of HU6, a controlled metabolic accelerator (CMA), for MASH. The majority of patients achieved an over 30% reduction in liver fat with no significant change in lean mass at any dose.
    • Altimmune also announced positive topline results of the phase 2b IMPACT trial (n=212), which evaluated dual GLP-1/glucagon RA pemvidutide versus placebo for MASH. At Week 24, a significantly higher percentage of participants taking pemvidutide 1.2 mg and 1.8 mg achieved MASH resolution without worsening of fibrosis compared to the placebo group (59% and 52%, respectively, vs. 19% with placebo).
    • South Korea-based D&D Pharmatech then announced positive safety and efficacy results from its ongoing 48-week phase 2 trial of DD01, a once-weekly dual GLP-1/glucagon RA. DD01 achieved a mean reduction of liver fat content of 62% versus 8% for placebo. Nearly half of all participants (49%) achieved normalization of liver fat fraction.
  • Throughout 2025, survodutide (a dual glucagon/GLP-1 RA), continued to be evaluated in phase 3 trials for MASH and obesity. The LIVERAGE (n=1,800) trial of survodutide in MASH with moderate or advanced fibrosis (stage 2 or 3) is expected to complete at the end of 2031; and the LIVERAGE-Cirrhosis (n=1,590) trial of survodutide in MASH with compensated cirrhosis (stage 4 fibrosis) is expected to complete in 2H29.
  • In October 2025, a post-hoc analysis of the SYNERGY-NASH trial evaluating once-weekly tirzepatide in participants with MASH and stage 2/3 fibrosis revealed further liver-directed benefit. 62.4% of people achieved MASH resolution without worsening of liver fibrosis versus 9.8% in placebo. A significantly greater percentage of participants taking tirzepatide (55%) saw an improvement in fibrosis without worsening of MASH versus those taking placebo (30%).
    • Responders for MASH resolution and fibrosis reduction showed greater decreases in body weight (p<0.001 and p=0.023, respectively). A1c reductions were also greater among both MASH (p<0.001) and fibrosis responders (p=0.004). Lastly, liver fat reduction and improved adipose insulin sensitivity was notably improved for MASH responders. Normalization of liver fat was a key mediator of both responder outcomes. Collectively, the findings suggest that tirzepatide’s effects on weight loss and metabolism contribute to disease modification in MASH.

9. Beyond opioids and status quo: Emerging therapies for neuropathic pain and limb health

This year, the field saw exciting advancements for microvascular complications, including diabetic painful neuropathy (DPN), peripheral artery disease (PAD), and adverse limb events. Therapeutic development for these complications has been stagnant for decades. Among the nine million people in the US with progressive DPN, 60% have tried multiple treatments, as most therapies do not provide sufficient relief, and a third have resorted to opioid treatments for short-term pain relief, which can increase the risk of opioid addiction. Despite these challenges, there has not been a new nonopioid treatment for DPN in the past two decades. Likewise, PAD affects 10-20 million people in the US, lowering quality of life due to pain, difficulty in walking, and amputation. However, the only treatment for claudication (muscle pain due to lack of oxygen) for people with PAD is cilostazol, which was FDA-approved in 1999. Vertex’s oral non-opioid NaV1.8 inhibitors, Lexicon’s pilavapadin (LX9211), and Novo Nordisk’s semaglutide have the potential to address these significant unmet needs.

• On DPN, Vertex is evaluating Journavx (suzetrigine), an oral, twice-daily NaV1.8 inhibitor, in two phase 3 trials, following positive phase 2 data (n=192), in which Journavx demonstrated statistically significant and clinically meaningful reductions in the numeric pain rating scale (NPRS) of over two points (out of a scale of 0-10). Given these results, the FDA granted Fast Track Designation for Journavx in peripheral neuropathic pain (PNP) and Breakthrough Therapy Designation in DPN. Vertex also assesses VX-993, an oral NaV1.8 inhibitor, in the phase 2 DPN trial (n=300). Separately, Journavx was launched for adults with moderate-to-severe acute pain, following FDA approval in January 2025.
  • Lexicon’s pilavapadin (LX9211), an oral, non-opioid AAK1 inhibitor for moderate-to-severe DPN, is also advancing to phase 3 trials in 2026. This follows a full readout of the phase 2b PROGRESS trial (n=496) results at EASD 2025, which showed that all pilavapadin doses, including placebo, reduced average daily pain score from baseline through Week 8. While the trial did not meet its primary endpoint (p=0.11), a post-hoc analysis excluding the highest dose (20 mg) arm achieved significance (p<0.04), supporting the 10 mg dose for future phase 3 studies. The company has scheduled an end-of-phase-2 meeting with the FDA for 4Q25, with written feedback expected in early 2026.
• On PAD, semaglutide significantly improved walking function and patient-reported outcomes in people with T2D and early-stage symptomatic PAD in the phase 3b STRIDE trial (n=792). As presented at ACC 2025, at Week 52, participants on semaglutide had 40 meters greater improvement from a baseline of 185 meters in maximum walking distance, compared to placebo. Furthermore, a post-hoc analysis found that increase in functional capacity did not correlate directly with weight or A1c changes, suggesting additional mechanisms driving functional PAD improvements (e.g. enhanced perfusion or vascular function).
  • Injectable and oral semaglutide was also associated with reduced major adverse limb events (MALE). A prespecified analysis from the SOUL trial (n=9,650) found that Rybelsus (oral semaglutide) reduced MALE by 30% in people with T2D, with similar benefits observed in participants with and without PAD. In another pooled analysis of the SOUL, FLOW, and STRIDE trials (n=13,975), semaglutide was associated with a ~30% reduction in limb events across patient subgroups. Taken together, findings support semaglutide as the first diabetes therapy to demonstrate significant limb-event reduction, irrespective of patient history of PAD.

10. Regulatory approvals for diabetic macular edema and diabetic retinopathy improve therapeutic access; commercialization efforts of anti-VEGF biosimilars continue

In 2025, treatment options expanded for eye complications, including neovascular (wet) age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy (DR). Susvimo (ranibizumab), Vabysmo (faricimab), and Eylea (aflibercept) currently lead the therapeutic landscape, with key biosimilars to reach commercialization in the near future and less-invasive treatment options also continually explored.

This year, Roche’s Susvimo (ranibizumab) 100 mg/dL, a refillable anti-VEGF eye implant, received approval for ocular complications related to diabetes.

• In February 2025, the FDA approved Susvimo (ranibizumab) 100 mg/mL for diabetic macular edema (DME), making it the first and only continuous delivery system available for this condition. The approval was based on one-year results from the phase 3 Pagoda trial (n=634), in which  Susvimo sustained vision improvements comparable to monthly 0.5 mg ranibizumab intravitreal injections.
• In May 2025, Roche announced that the FDA approved its effective therapy Susvimo (ranibizumab) 100 mg/dL for diabetic retinopathy (DR) after submission in April 2024. The PAVILION trial (n=174) evaluated the safety and efficacy of Susvimo for DR. At one year, participants who received Susvimo, refilled every nine months, saw reduced severity in eye damage compared to those receiving monthly clinical observation and treatment with anti-VEGF injections as needed
• In September 2025, Roche also received CE-Mark for Contivue, a port delivery platform for refillable anti-VEGF therapy Susvimo (ranibizumab). Contivue is surgically implanted into the eye, continuously delivering Susvimo over six to nine months, after which the medication is refilled by a healthcare professional. The CE-Mark of Contivue was based on the pivotal phase 3 Archway trial (n=415), and two supportive studies, the phase 2 LADDER study (n=225) and the open-label long-term extension phase 3 Portal study (n=1,000).

Vabysmo (faricimab), also manufactured by Roche, also demonstrated long-term safety this year.

• In September 2025, Roche announced new long-term data on Vabysmo (faricimab) at the Euretina Congress, reinforcing its efficacy, safety, and durability in treating neovascular or “wet” age-related macular degeneration (nAMD). The AVONELLE-X and SALWEEN studies demonstrated that the extended dosing of Vabysmo may offer potential to reduced treatment burden for nAMD.

Regeneron’s Eylea (aflibercept) faced both manufacturing setbacks in the US and a key label extension in Europe.

• In April 2025, the FDA issued a complete response letter (CRL) for anti-VEGF Eylea HD (aflibercept 8 mg). The CRL provided a response to the supplemental Biologics License Application (sBLA) of extending the maximum dosing interval (up to every 24 weeks) for Eylea HD across all approved indications: (i) wet age-related macular degeneration (wAMD); (ii) diabetic macular edema (DME); and (iii) diabetic retinopathy (DR). The CRL did not cite any issues with the safety or efficacy of Eylea HD in its current approved indications and dosing regimens and was related to manufacturing issues.
• In June 2025, the European Commission granted a label extension for Eylea HD (aflibercept 8 mg) in the EU with extended treatment intervals of up to every six months. Eylea is an anti-vascular endothelial growth factor (VEGF) treatment injection for neovascular or wet age-related macular degeneration (nAMD) and visual impairment due to diabetic macular edema (DME). With this approval, Eylea HD became the first therapy with a six-month treatment interval for the treatment of nAMD and DME in the EU.

Key anti-VEGF biosimilars Yesafili and Eydenzelt became closer to commercial launch in 2025.

• In April 2025, Biocon Biologics finalized a settlement and license agreement with Regeneron, enabling US commercialization of the vascular endothelial growth factor (VEGF) inhibitor Yesafili (aflibercept-jbvf). Yesafili is indicated for wet age-related macular degeneration (AMD), DME, diabetic retinopathy (DR), and retinal vein occlusion (RVO). The therapy is the first FDA-approved interchangeable biosimilar to Eylea (aflibercept). Under the agreement, Biocon can launch Yesafili in the US in 2H26 or earlier. The FDA approved Yesafili in May 2024 as an interchangeable biosimilar to Eylea following results from the phase 3 INSIGHT study.
• In October 2025, the FDA approved Celltrion’s Eydenzelt (aflibercept-boav), a biosimilar of Regeneron and Bayer’s anti-VEGF therapy Eylea (aflibercept), for neovascular (wet) age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy (DR). The FDA’s decision was supported by clinical data from a 52-week, head-to-head phase 3 study (n=348) among patients with DME. Eydenzelt met equivalence criteria in visual acuity improvement and showed comparable safety, pharmacokinetics, and immunogenicity to Eylea. Eydenzelt was also approved by the European Commission in February 2025.

While intravitreal injections remain the standard of care for AMD, diabetic retinopathy, DME, and RVO, work to explore less-invasive alternatives continues.

• In May 2025, UNITY Biotechnology announced full results of the 36-week phase 2b ASPIRE trial (n=52), which evaluated intravitreal injections of small molecule UBX1325 (foselutoclax) in people with diabetic macular edema (DME), compared to anti-VEGF Eylea (aflibercept 2 mg). Results of the ASPIRE trial (n=52) showed that UBX1325 improved visual acuity (VA) by 5.2 letters (vs. 4.8 letters with aflibercept) and 5.5 letters (vs. 5.3 letters) from baseline at Weeks 24 and 36, respectively – this improvement is equivalent to roughly one additional line on an eye chart.
• In July 2025, Boehringer Ingelheim and Re-Vana Therapeutics announced a collaboration and license agreement to develop extended-release therapies for eye diseases. Boehringer Ingelheim plans to combine its eye disease candidates with Re-Vana’s gradual release technology to release treatments slowly over six to 12 months, reducing the frequency of eye injections.

11. Obesity treatment has a powerhouse year with lots of excitement for next: New approvals, readouts, and clinical frameworks for incretins, amylin, and beyond

Obesity and weight management were at the center of clinical development and discussions this year. In the treatment landscape, Wegovy (semaglutide) and Zepbound (tirzepatide) continued to record multi-billion sales each quarter, as they demonstrated benefits beyond weight loss and metabolic health and expanded into cash pay and global markets. In the pipeline, other late-stage candidates, including Lilly’s orforglipron (oral GLP-1 RA) and Novo Nordisk’s CagriSema (fixed dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg), delivered robust phase 3 results, setting paths for regulatory decisions, while earlier-stage therapies continue to advance in the pipeline, while differentiating themselves from existing therapies. Along with the innovations, the ADA Standards of Care 2026 and conference symposia strengthened important clinical insights, such as the need for personalized titration regime, strategies for lean mass preservation, and underlying causes of heterogeneity in treatment responses.

• Major topline results and trial readouts showed promise in late-stage incretin-based candidates. In December 2025, Lilly announced topline results of the 68-week phase 3 TRIUMPH-4 trial (n=405) of once-weekly retatrutide (triple GLP-1/GIP/glucagon RA), which showed up to 29% weight loss and significant pain reduction in people with obesity and osteoarthritis. In the phase 3 REDEFINE-1 trial (n=3,417), Novo Nordisk’s CagriSema conferred up to 20% weight loss and cardiovascular (CV) benefits in people with obesity without T2D. In the phase 3b STEP UP trial (n=1,407), high-dose semaglutide 7.2 mg conferred 21% weight loss in adults with obesity, leading to FDA submission and positive recommendation by the EMA. Excitingly, Innovent Biologic’s mazdutide (GLP-1/glucagon RA), was approved in China for obesity as the second dual incretin-based therapy based on the phase 3 GLORY-1 trial (n=610), which showed 15% weight loss. Once-monthly MariTide (maridebart cafraglutide; GLP-1 RA and GIP receptor antagonist) demonstrated 20% weight loss in the phase 2 trial (n=592) but with high GI adverse events. Jiangsu Hengrui Pharmaceutical’s HRS9531 (dual GLP-1/GIP RA) conferred 23% weight loss in Chinese adults with overweight or obesity in a phase 2 trial (n=60).
  • On oral agents, Novo Nordisk’s Wegovy pill (once-daily oral semaglutide 25 mg) received FDA approval as the first oral incretin-based therapy for weight management. Wegovy pill is indicated for weight loss, long-term weight maintenance, and cardiovascular (CV) risk reduction. The approval is based on the phase 3 OASIS-4 trial (n=307), in which oral semaglutide 25 mg conferred up to 14% weight loss (vs. 2%) at 64 weeks, and SELECT trial (n=17,604), which showed 20% reduction in MACE with injectable semaglutide. As per the Most-Favored Nation pricing, Wegovy pill will be offered at $150 per month on TrumpRx, the government’s direct-to-consumer platform.
  • In the pipeline, Lilly’s orforglipron led to 11% weight loss in the phase 3 ATTAIN-1 trial (n=3,127), with a launch expected in 2026 pending approval. Novo Nordisk submitted high-dose oral semaglutide 25 mg for obesity in the US and the EU based on the phase 3 OASIS-4 trial (n=307), which showed 14% weight loss.
• On other emerging therapies, long-acting amylin agonists, like Novo Nordisk’s cagrilintide, Lilly’s eloralintide, and Zealand/Roche’s petrelintide, received spotlights as potentially foundational weight loss therapies that do not cause significant GI side effects. At EASD 2025, a post-hoc analysis of the phase 3 REDEFINE-1 trial (n=3,417) found that cagrilintide achieved an average weight loss of 12%, compared to 2.3% with placebo at Week 68. In a phase 2 trial (n=263), as presented at ObesityWeek 2025, all doses of eloralintide demonstrated statistically significant weight loss, ranging from 9.5% to 20.1%, compared to 0.4% with placebo and favorable tolerability profile. In March, Zealand and Roche entered partnership to co-develop and co-commercialize amylin analog petrelintide for obesity. The candidate is currently evaluated in the phase 2 ZUPREME-1 and ZUPREME-2 trials.
• Clinical discussions included the importance of personalizing titration schemes, challenges of rapid weight loss, and concerns about lean mass preservation. On the former, the ADA Standards of Care 2026 newly added a recommendation that stresses the importance of personal dose titration to balance efficacy, health benefits, and tolerability. This inclusion echoes sentiment from a symposium from ADA 2025 on the new Standards of Care for Obesity, at which speakers unequivocally emphasized that patients have different treatment goals and respond to drugs differently, and that maintenance dosage for obesity pharmacotherapy should be tailored to individuals.
  • On the heterogeneity in patients’ treatment responses, a post-hoc analysis of the SURMOUNT-5 trial (n=751) found that rapid responders to tirzepatide and semaglutide were more likely to be female and have lower weight at baseline. Speaker Dr. Louis Aronne (Weill Cornell) challenged the audience that rapid response may not be necessarily “better,” and proposed that the current titration regimen might even be “excessive” in some patients. More recently, at WCIRDC 2025, Dr. Tracey McLaughlin (Stanford University) shared her hypothesis on why the pathophysiology and treatment response for obesity are heterogenous. She said that visceral fat, inflammation, and impaired adipogenesis are key drivers of insulin resistance, which determines whether an individual with overweight or obesity also have metabolic dysfunction.
  • On lean mass preservation, clinicians continue to debate its clinical significance. Dr. Sameul Klein (Washington University at St. Louis) argues that muscle mass loss is natural and clinicians should instead focus on whether weight loss improved cardiometabolic health, physical function, and quality of life; meanwhile, Dr. Richard Pratley (AdventHealth) states that muscle mass loss can be critical for older and more vulnerable adults, who are at higher risk of falls. Multiple interventions are in development for muscle mass preservation. In the phase 2b COURAGE trial (n=1,005), trevogrumab (anti-GDF8/anti-myostatin), with or without garetosmab, significantly improved weight loss quality when added to semaglutide. Likewise, in the phase 2 BELIEVE trial (n=507), bimagrumab (monoclonal antibody blocking activin type II receptors) increased muscle mass and decreased fat mass when added to semaglutide, though Lilly discontinued the trial in September 2025.

12. Reframing T2D care: “Precision” therapies and hypercortisolism

2025 brought a renewed attention to the heterogeneity of T2D, and, with it, a push toward more targeted (not to mention, mechanistically-informed) treatment strategies. Two major developments reframed how the field thinks about difficult-to-treat T2D: the emergence of hypercortisolism as a modifiable contributor to challenging glycemic management, and the rise of precision therapies aimed at restoring beta cell function.

• The CATALYST trial (n=1,113) spotlighted hypercortisolism as a clinically relevant and underdiagnosed driver of difficult-to-manage diabetes. In Part 1 of the trial, nearly 25% of participants with difficult-to-treat T2D were found to have hypercortisolism, with prevalence rising to 37% among those on three or more antihypertensives. In Part 2, treatment with mifepristone, a glucocorticoid receptor antagonist, led to a 1.5% A1c reduction over 24 weeks, alongside meaningful reductions in insulin use, body weight, and waist circumference. Notably, one-third of participants with hypercortisolism had adrenal abnormalities seen on imaging, suggesting a structural basis for dysregulation in a subset of patients.
  • KOL commentary at ADA 2025 reinforced the clinical implications. Dr. Ralph DeFronzo (UT Health San Antonio) emphasized that hypercortisolism often presents without classic symptoms but instead manifests as some combination of the “big four”: (i) uncontrolled T2D; (ii) hypertension; (iii) obesity; and (iv) osteoporosis, which are commonly seen in endocrine practice. He called for inclusion of hypercortisolism in the “noxious nine” factors driving hyperglycemia. In addition, Dr. John Buse (University of North Carolina) advocated for routine screening in patients who struggle to reach glycemic targets.
• In October 2025, Biomea Fusion announced results of the phase 2 COVALENT-111 (n=163) trial. In the study, icovamenib (BMF-219), a covalent menin inhibitor, conferred sustained A1c reductions in insulin-deficient subgroups of people with T2D, including those on GLP-1 RAs who had not achieved glycemic goals. At Week 52, icovamenib conferred up to 1.5% A1c reduction after just 12 weeks of dosing, with no treatment-related serious adverse events. The agent is designed to promote beta cell proliferation and function, offering a potential disease-modifying approach for patients with severe insulin deficiency. This advancement reflects the field’s transition from broad anti-hyperglycemic approaches to precision strategies that address underlying pathophysiology for specific subgroups. 

Top Ten Most Read Closer Look Reports in Therapy

1. Obesity Drug Competitive Landscape – December 18, 2025 – see inside for the overview of obesity candidates in preclinical to phase 3 stages
2. Type 1 diabetes cures and prevention competitive landscape – September 9, 2025 – read more here for candidates in development for beta cell replacement, immune therapy, or other approaches
3. vTv Therapeutics 3Q25 – November 11, 2025 – phase 3 CATT1 trial for cadisegliatin in T1D; $80 million private placement bolsters funding
4. GLP-1 Mono, Dual, and Tri-Agonist Competitive Landscape – October 2, 2025 – featuring an ever expanding list of the GLP-1 RAs (injectable and oral), dual agonists, and tri-agonists
5. Lilly 4Q24 – February 6, 2025 – diabetes sales total $9.1B in 4Q24 (+59%) and $29.5B in 2024 (+50%), driven by Mounjaro and Zepbound; comments on compounding and patient access program; major focus on oral GLP-1 orforglipron for obesity, T2D, OSA, and hypertension
6. Tirzepatide demonstrates noninferiority in MACE reduction compared to dulaglutide in P3 SURPASS-CVOT trial – July 31, 2025 – tirzepatide confers 8% reduction in MACE, though statistically insignificant, and reduces all-cause mortality by 16%
7. Novo Nordisk 2Q25 – August 6, 2025 – diabetes/Obesity portfolio totals $11.3B (+17% CER, -2% sequentially); updates on amycretin, CagriSema, MASH; where might legal actions against compounding go?
8. Lilly announces positive topline phase 3 ACHIEVE-1 results of oral GLP-1 RA orforglipron in T2D – April 17, 2025 – orforglipron demonstrates up to 1.6% A1c reduction and 8% weight loss
9. Semaglutide 7.2 mg confers superior weight loss compared to semaglutide 2.4 mg in phase 3 STEP UP trial – January 2025 – higher-dose semaglutide achieved weight loss of 20.7% at Week 72, compared to 17.5% with semaglutide 2.4 mg and 2.4% with placebo
10. Post hoc analysis of SURMOUNT-2 reveals weight reduction with tirzepatide varies by baseline A1c – August 22, 2025 – Reduced glucosuria from improved glycemic management may limit weight loss in patients with high baseline A1c

Most Unexpected News/Biggest Surprises 

Incretins

1. Novo Nordisk submits unsolicited ~$9 billion bid to acquire Metsera; offer may trigger “Superior Company Proposal” notice in Pfizer’s existing acquisition agreement

2. Most-Favored-Nation Pricing expands to offer GLP-1 RAs at $245/month through Medicare and Medicaid plus significant discounts through TrumpRx

3. CMS announces negotiated prices for 15 drugs in the second round of Medicare Drug Price Negotiation Program, including semaglutide

Complications Management

1. Vertex announces FDA approval of Journavx (suzetrigine) for moderate-to-severe acute pain; of interest to those with diabetes peripheral neuropathy, this represents first new pain medication class to receive FDA approval in 20+ years

2. Novo Nordisk’s semaglutide did not confer statistically significant reduction in Alzheimer’s disease progression in phase 3 evoke trials

SGLT inhibitor

1. In the UK, the NICE draft guidance recommends SGLT-2 inhibitors as a first-line therapy with or without metformin for the general population with T2D

2. Lexicon submits additional data for Zynquista (sotagliflozin) in continued efforts to address FDA CRL and support NDA resubmission

3. NEJM publishes full results of the phase 2 CONFIDENCE trial of finerenone and an SGLT-2 inhibitor in CKD and T2D

Insulin

1. Novo Nordisk resubmits insulin icodec (Awiqli) to the FDA for T2D; once-weekly insulin already approved in the EU, Japan, and China

T1D

1. Sanofi’s Tzield for the treatment of stage 3 T1D receives first-ever national priority voucher

2. Vertex shares updates on T1D programs; while VX-264 compound discontinued due to lack of efficacy, look for VX-880 regulatory submission in 2026

3. FINE-ONE full results: Finerenone meets primary endpoint, reducing UACR by 25% in people with T1D and CKD

4. ADA publishes 2026 Standards of Care, with recommendations for incretin-based therapies in people with T1D

Obesity

1. Lilly discontinues phase 2 trial of bimagrumab and tirzepatide in people with overweight or obesity and T2D

Big Picture

Key Questions for 2026

T1D screening and monitoring

1. What initiatives and efforts could be implemented to increase more precise screening and detection of T1D according to subgroups (e.g., genetic risk factors)?
2. How will the US Preventive Service Task Force (USPSTF) update its recommendations on screening and preventive care, based on Sanofi’s submission on this importance?

Overall health and comorbidity management

1. How could trials integrate more real-world evidence to reflect the ongoing management of overall health outcomes, including comorbidities?
2. What risk mitigation strategies could help increase education and awareness about therapies and technologies emerging in the space?

Direct-to-consumer market, compounding, and US drug pricing

1. What measures are telehealth companies using to ensure that GLP-1 RAs are prescribed with comprehensive clinical review of patients and without company-employed prescriber bias?
2. How has FDA’s “green list” import alert affected the safety and quality of compounded products?
3. How will the official launch of TrumpRx affect sales and uptake for diabetes and obesity treatment?
4. For companies participating in the Most-Favored-Nation pricing agreement, will price reductions extend to other treatments in their portfolio? What are the inclusion criteria?
5. How might the implementation of the discounted prices via the Medicare Drug Price Negotiation Program affect demand for the selected drugs? How will these policy changes impact innovation?
6. Will MFN pricing impact global pricing in any material way in 2026?

Regulatory changes

1. If the FDA moves toward a single‑trial requirement for approval, where might this happen? Might it only be primarily in areas like oncology? Might it include only very uncontroversial trials in diabetes and obesity? How could, in any therapeutic area, this reshape clinical trial design, evidence expectations, and regulatory strategy? In chronic, heterogeneous diseases such as diabetes and obesity, might there be a different approach, particularly given the historical reliance on multiple parallel trials – for example, the STEP program for Novo Nordisk’s Wegovy and Lilly’s SURMOUNT program for Zepbound to demonstrate consistency across populations, endpoints, and geographies?
2. In a single‑trial paradigm, what new expectations might emerge around trial size, statistical powering, confirmatory evidence, real‑world data, and diversity across age, sex, race/ethnicity, and comorbidity profiles to ensure that one study can adequately support a broad, real‑world use?
3. Given the FDA’s longstanding requirement for cardiovascular outcomes trials (CVOTs) for diabetes therapies since 2008 and the substantial patient benefit derived from these large safety studies, how might the potential single‑trial approval standard apply to diabetes drugs?
4. Could a single‑trial rule apply only to established molecules seeking new indications (e.g., heart failure), while new molecular entities in diabetes and obesity continue to require multi‑trial programs and extensive safety datasets?

Leadership change

1. How will Novo Nordisk’s newly reconstituted Board – led by Mr. Lars Rebien Sørensen and shaped by the Foundation’s push for faster and more decisive governance – balance the need for accelerated strategic action in a rapidly shifting US market with the equally critical need for stability and continuity?
2. On the private company front, it was interesting to see both a new chairman at Boehringer Ingelheim, Shashank Deshpande, as well as a key competitive hire on the senior management side, Brian Hilberdink from Novo Nordisk?

Themes

1. Screening for T1D remains a key priority, with emphasis on education and awareness

2025 included several highlights on screening to highlight the importance of early intervention and monitoring. The field has consistently emphasized the importance of T1D autoantibody screening through efforts like Breakthrough T1D’s submission to the US Preventive Services Task Force (USPSTF) in May 2025. As background, the application included recommendations for early, population-wide T1D screening, with an emphasis on individuals with an increased genetic risk. Breakthrough T1D believes that a formal recommendation from the USPSTF on this submission would enhance screening and early diagnosis, ultimately improving health outcomes for many patients. In November 2025, Sanofi hosted a webinar to discuss the publishing process, including steps that will lead to clinical treatment recommendations. The webinar also explained the value of education for early screening, particularly for pre-symptomatic populations at high risk of T1D.

• Emerging recommendations for screening, monitoring, and managing. Following last year’s critical publication of “Consensus for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes” in Diabetes Care and Diabetologia, several publications have reinforced the importance of autoantibody screening. For example, The Lancet Diabetes & Endocrinology published a pragmatic framework for providing care to adults who have tested positive for one or more islet autoantibodies. This publication addresses the variability, particularly for adults with a lower risk of T1D progression and high prevalence of baseline dysglycemia, and provides a three-year clinical roadmap for adults with positive islet autoantibodies.
• Evidence reinforces the importance of autoantibody screening. Focusing on early intervention, Diabetes Care published a study comparing autoantibody screening and T1D outcomes between adults and children. In the study, progression to stage 3 T1D was lower in adults with single autoantibody positivity or stage 1 T1D in children, resulting in a five-year risk of 8% for adults with single autoantibody positivity versus 22% for children with stage 1 T1D. However, adults with stage 2 T1D from an initial staging OGTT had comparable five-year progression risks to children, which was 78% for both groups. This report provided further evidence that adult relatives with positive autoantibodies have distinct trajectories and progression risks compared to children, suggesting the need for tailored monitoring and intervention strategies for T1D classification.
• Remaining unmet needs in T1D. In honor of World Diabetes Day in November 2025, Breakthrough T1D released its first-ever “State of T1D” report, synthesizing data from epidemiological studies, national surveys, and Breakthrough T1D-supported research projects to provide a comprehensive overview of the global and US burden of T1D. Breakthrough T1D reported that approximately 1.5 million of those living with T1D reside in the US, including nearly 200,000 children under the age of 20. As this number continues to rise, the need for T1D screening programs and a commitment to T1D research becomes increasingly evident.
• Ongoing efforts to increase education and awareness. We continue to reflect on our conversation with notable leaders from Sanofi in May 2025, during which we discussed Sanofi’s efforts to raise awareness among primary care physicians, pediatricians, patients, and their immediate family members with T1D. We particularly appreciated how education remains a key strategy for increasing T1D detection and access to potential interventions. Focusing on education and awareness, Breakthrough T1D has also announced that nearly 82% of its recent $1.2 billion funding has been dedicated to T1D cures. Furthermore, organizations like Beyond Type 1 continue to invest resources in support of breakthroughs and improved patient outcomes. In November 2025, Beyond Type 1 celebrates its 10^th anniversary with the Beyond Limits event, which brought together the T1D community, encouraging people with diabetes to grow “beyond their diagnosis, beyond their barriers, and beyond expectations.”

2. Structural changes in pharmaceutical and tech giants: Spin-off of MiniMed and restructuring of Novo Nordisk indicative of broader industry shifts

This year, there were significant changes to diabetes technology and pharmaceutical companies. In diabetes technology, two major care businesses announced plans to separate from their parent organizations: MiniMed is spinning out from Medtronic, while Ypsomed’s mylife Diabetes Care AG was sold to TecMed. In CGM, Dexcom also announced a CEO succession plan, with current President and COO (as well as interim CEO) Mr. Jake Leach set to succeed Mr. Kevin Sayer as CEO effective next year. Novo Nordisk similarly underwent sweeping leadership transitions to the CEO and Board of Directors, as well as overall restructuring of the company. After several quarters of underperformance due to rising competition in the GLP-1 RA market, compounding business, and pricing pressure, the company is focused on redirecting resources to new “growth opportunities” in diabetes and obesity to regain its competitive leadership.

• In May, Medtronic announcedthat it will separate its Diabetes division into a standalone, publicly traded company – MiniMed – by November 2026. Ms. Que Dallara (current Diabetes President and EVP) will serve as its CEO. All steps taken so far have supported its preferred separation pathway, led by an initial public offering (IPO) followed by a split-off. Mr. Geoff Martha implied that the separation is driven by lower margins and the need for future investment across the business and differing business models – the Diabetes business operates mainly as business-to-consumer (B2C), differing from the rest of the company’s portfolio. He said this move will allow Medtronic to streamline its operations, generating proceeds that will support further investment in its higher-growth, higher-margin areas, while simultaneously enabling the new company to devote more resources to developing the diabetes portfolio Medtronic was advancing. Ms. Dallara echoed these sentiments, saying in an interview at ADA that she thinks: “the most exciting thing to us is that we can bring innovations fast for patients. We control our own destiny.” Medtronic filed a registration statement on Form S-1 with the US Securities and Exchange Commission (SEC) for an IPO of its Diabetes business in December, which detailed MiniMed’s financial profile and pipeline supporting independent operation.
• Dexcom announced its CEO succession plan in July, with current President and COO Mr. Leach set to succeed Mr. Sayer as the company’s next CEO effective January 1, 2026. Mr. Leach, who has been with Dexcom for 21 years following experience at MiniMed and Medtronic, has overseen the company’s CGM platforms since their first commercial launch. His promotion follows a series of leadership roles, including EVP & CTO (2018-2022), EVP & COO (2022-2025), and his May 2025 appointment as President & COO with oversight of corporate strategy and development. During Q&A after the announcement, Mr. Leach outlined his vision for the company’s next chapter, highlighting three strategic pillars: (i) global access; (ii) innovation; and (iii) scale and implementation. He pointed to substantial opportunity for Dexcom globally, highlighting both the health and cost benefits that broader adoption could deliver to international healthcare systems. On innovation, Mr. Leach emphasized his excitement in providing real value to Dexcom’s customers – an increasingly divers userbase, including people with T2D not on insulin, prediabetes, and those focused on metabolic health.
• Ypsomed announced in August 2025 that it has successfully completed the sale of its Diabetes Care business (named mylife Diabetes Care AG) to TecMed. The sale, totaling up to CHF 420 million ($514 million), was originally announced in April 2025. TecMed, founded in late 2020 and owned by Mr. Willy Michel (the father of Ypsomed’s CEO Mr. Simon Michel), is an insulin infusion company that will assume control of Ypsomed Diabetes Care’s operations and assets, including the mylife Loop AID system. The sale did not include Ypsomed’s subcutaneous self-injection products, with the company retaining ownership of its pens and auto injectables as it increasingly targets the biologics and biosimilars market.
• Novo Nordisk appointed Mr. Maziar Mike Doustdar, a former EVP of International Operations, as the new President and CEO of the company, effective August 2025. This followed the announcement in May 2025 that Mr. Lars Fruergaard Jørgensen would step down as the CEO due to market challenges, declines in stocks since mid-2024, and a decision by its biggest shareholder, Novo Nordisk Holdings. Indeed, the company had lowered the 2025 guidance four times this past year, with sales growth now expected at 8-11%, down from 16-24% originally projected in January 2025.
  • Since becoming the new CEO, Mr. Doustdar led several restructuring efforts to redirect resources to new “growth opportunities” in diabetes and obesity. In September, the company announced its plans to cut ~9,000 jobs globally (~12% of its workforce). In October, the company terminated several stem cell research, including its search for T1D cure. Meanwhile, Novo Nordisk pursued multiple partnerships and acquisitions in the cardiometabolic field, such as its $5.2 billion acquisition of MASH-focused Akero Therapeutics, collaborations for drug development, and an unsuccessful unsolicited $10 billion bid to acquire Metsera.
  • In November 2025, Mr. Lars Rebien Sørensen, former CEO and current Chair of the Board of Novo Nordisk Foundation, was elected as the new Chair of the Board of Directors (BOD) in an Extraordinary General Meeting. This leadership transition follows announcement that former BOD Chair Mr. Helge Lund and several board members resigned amid an unresolvable dispute between the BOD and Novo Nordisk Foundation about the future composition of the board and the governance principles of the company. Mr. Sørensen aims to prioritize: (i) supporting Novo Nordisk regain its competitive leadership and (ii) preparing for the future board leadership in the next two-to-three years.
• Also on leadership, Dr. Rita Kalyani (Johns Hopkins) was appointed as the new Chief Scientific & Medical Officer (CSMO) of the American Diabetes Association (ADA) starting in August 2025, following Dr. Bob Gabbay’s resignation in July 2024. At ADA 2025, Dr. Kalyani delivered the ADA’s President of Medicine and Science address, offering a comprehensive look at the past, present, and future of diabetes care and how she envisions the ADA and its members to shape diabetes research, clinical care, and policy.

3. Major M&As for MASH and obesity: The race towards the next-generation therapies 

The fall of 2025 was a dynamic period for mergers and acquisitions (M&A) in the cardiometabolic field, as companies raced to the next-generation treatments for obesity and metabolic dysfunction-associated steatohepatitis (MASH). The acquisitions signal the field’s broader focus in liver health alongside glycemic management, weight loss, and cardiovascular health.

• In September 2025, Roche agreed to acquire San Francisco-based 89bio for up to $3.5 billion. 89bio’s lead drug candidate is pegozafermin, an FGF21 analog currently in three phase 3 trials for the treatment of moderate to severe fibrosis (fibrosis score F2-F3)[1] in MASH, cirrhosis (F4) related to MASH, and severe hypertriglyceridemia. The acquisition reflects Roche’s commitment to expanding its cardiometabolic portfolio. Earlier in March 2025, Roche partnered with Zealand to develop and commercialize Zealand’s petrelintide (long-acting amylin analog) and explore combination therapies, such as petrelintide with Roche’s dual GLP-1/GIP RA, CT-388, for the treatment of overweight and obesity.
• In October 2025, Novo Nordisk announced the acquisition of Akero Therapeutics, developer of FGF21 (fibroblast growth factor 21) analog efruxifermin. Akero’s lead therapy is being evaluated in multiple phase 3 trials for compensated cirrhosis (F4) and pre-cirrhosis (F2-F3), respectively, in people with MASH. The definitive agreement has a value of up to $5.2 billion in cash.
• In September 2025, Pfizer agreed to acquire Metsera for up to $7.3 billion. This set off a series of events in a subsequent bidding war, whenon October 30, Novo Nordisk submitted an unsolicited ~$9 billion acquisition offer. However, in November 2025, Metsera entered into an amended merger agreement worth up to $10 billion with Pfizer. Following lawsuits and Federal Trade Commission (FTC) involvement, Pfizer successfully acquired the company and with it: (i) MET-097i, a once-monthly GLP-1 RA; (ii) MET-233i, a once-monthly amylin analog; and (iii) oral GLP-1 RA candidates. The high-cost, highly public acquisition dispute signals the importance of liver health in 2025.

4. Inflation Reduction Act and Most-Favored-Nation policy: US government reaches price negotiations with pharmaceutical companies

Continuing last year’s momentum toward lower drug prices in the US, the government reached negotiations with pharmaceutical companies under the Medicare Drug Price Negotiation Program (MDPNP) and the Most-Favored-Nation (MFN) policy. See the table below for drug price changes from these programs.

• In November 2025, the Centers for Medicare and Medicaid Services (CMS) negotiated prices for the 15 drugs included in the second round of MDPNP, which will become effective on January 1, 2027. The program was established by the Inflation Reduction Act of 2022, which requires that CMS negotiates prices with drug manufacturers for brand-name drugs without generic or biosimilar competition that are covered by Medicare Parts B or D. Only small molecules approved for at least seven years and biologics approved for at least 11 years are eligible for inclusion. Per negotiation, Novo Nordisk’s three semaglutide products – Ozempic, Rybelsus, and Wegovy – will face a 71% cut to their list prices, dropping from ~$950 per month in 2024 to $274 in 2027. Lilly’s DPP-4 inhibitor Tradjenta will be $78 per month, down 84% from $488, while Merck’s DPP-4 inhibitor/biguanide Janumet and Janumet XD will cost $80 per month, down 85% from $526 per month.
  • The negotiated prices from the first round of MDPNP will become effective soon on January 1, 2026. This includes: (i) AstraZeneca’s SGLT-2 inhibitor Farxiga; (ii) Merck’s DPP-4 inhibitor Januvia; (iii) BI/Lilly’s SGLT-2 inhibitor Jardiance; and (iv) Novo Nordisk’s rapid-acting insulins NovoLog and Fiasp, which will face a 66-79% cut from the list price. See the table below for specific changes.
  • Looking forward, the MDPNP will expand to include 15 additional drugs in 2028 and 20 additional drugs for 2029 and following years. Drugs selected for the MDPNP will continue to be announced in February two years before when the negotiated prices will take effect.
• In November 2025, the White House announced an expansion of the Most-Favored-Nation (MFN) pricing to offer GLP-1 RAs at $245 per month through Medicaid and Medicaid, as well significant discounts through TrumpRx. Medicare will have a direct deal with Novo Nordisk and Lilly to access treatments like Mounjaro (tirzepatide for T2D), Ozempic (semaglutide for T2D), Wegovy (semaglutide for obesity), and Zepbound (tirzepatide for obesity) for $245/month, for which Medicare beneficiaries will have a co-pay of $50 per month. State Medicaid programs will be able to access these medications at the same price. The new price changes are expected to take effect by mid-2026 for Medicare users but vary on a state-by-state basis for Medicaid patients.
  • Moreover, the government will launch TrumpRx, the government’s direct-to-consumer platform, in January 2026. As part of the MFN negotiations, drugs will be offered at discounted prices, including: (i) Wegovy at $350 per month; (ii) Wegovy pill at $150 per month; and (iii) Zepbound and orforglipron (upon approval) at $346 per month.
  • In December 2025, the government announced additional agreements with nine pharmaceutical companies for similar cost reductions. The drugs included in this agreement ranges from insulin and DPP-4 inhibitors to PCSK-9 inhibitors, as shown in the table below.
  • As background, in May 2025, the Trump Administration signed an executive order requiring pharmaceutical companies to align US drug prices with those in other developed nations. The executive order was first issued on a voluntary basis, with reinforcement planned if progress was not made. Since May, federal health agencies have published policy releases referencing the directive, and the administration has continued to meet with manufacturers to evaluate potential MFN options. On July 31, the US government issued a letter regarding the directive to 17 pharmaceutical companies including Amgen, Pfizer, Lilly, Novo Nordisk, AstraZeneca, and Regeneron. In the letter, President Trump reaffirmed the MFN pricing executive order and directed companies to comply within 60 days.

Table 1: Negotiated Prices for Diabetes and Obesity Medications

5. Direct-to-consumer market expands amid continued compounding business and pricing pressure

This past year, the GLP-1 RA market in the US shifted rapidly with compounding practices, pricing pressure from the government, and direct-to-consumer sales. While the FDA announced that the shortage of semaglutide and tirzepatide were resolved in in February 2025 and December 2024, respectively, mass compounding of “personalized” and more affordable drugs has persisted. For example, Hims & Hers sell compounded semaglutide at $199 per month, while MDEXAM and Curex offer compounded tirzepatide at $258 and $199 per month. Many of these companies add ingredients like vitamins to “personalize” treatments. In a 2Q25 call, Novo Nordisk estimated that approximately one million patients are on compounded GLP-1 RAs in the US and acknowledged that compounding business has negatively impacted its performance.

• To increase access to their drugs, both Novo Nordisk and Lilly launched their direct-to-consumer platforms, NovoCare Pharmacy and LillyDirect, which sell all approved doses of Wegovy, Ozempic, and Zepbound vials at discounted cash prices. After the two companies reached a deal with the government to implement Most-Favored-Nation pricing starting in mid-2026, Novo Nordisk further cut self-pay price of Wegovy to $349 per month in November 2025, while Lilly lowered the price of Zepbound vials to $299-$449 per month in December 2025. These prices reflect up to ~75% reduction from the list prices of $1,349 and $1,086 per month for Wegovy and Zepbound, respectively. Both companies shared the promise of direct-to-consumer marketing, as it offers patients with limited insurance coverage a more affordable option. In 3Q25, Novo Nordisk said that telehealth and retail cash channels account for ~10% of total Wegovy prescriptions (~26,000). Lilly similarly shared that Zepbound vials comprised nearly 30% of TRx and over 45% of new prescriptions in 3Q25.
  • Novo Nordisk and Lilly continued to expand partnerships across telehealth companies and retail pharmacies to broaden the reach of their cash channels. Novo Nordisk extended its cash offering to CVS, Costco, and Walmart, as well as several telehealth companies like WeightWatchers, Ro, and LifeMD. In October 2025, Lilly entered its first retail collaboration with Walmart Pharmacy to launch a pick-up option for people with valid prescriptions to single-dose Zepbound vials.
• The FDA introduced more regulations to ensure safety of compounded products. In September 2025, the FDA issued a “green list” import alert to regulate GLP-1 RA active pharmaceutical ingredients (APIs) from foreign facilities. The green list includes APIs from facilities that the FDA has inspected or evaluated to have met the US manufacturing standards. APIs from facilities not on the list would be subject to detention without physical examination (DWPE), for which the facilities are required to provide evidence that manufacturing and distribution of APIs follow the Current Good Manufacturing Practice (CGMP) requirements. This decision follows FDA’s investigation that many compounded GLP-1 RAs are manufactured with bulk APIs sourced from China, India, and Europe and that 21% of foreign API sites (10 of 48 inspected) are non-compliant with CGMP standards.
  • To further regulate compounding business, Reps. Rudy Yakym (R-IN) and André Carson (D-IN) introduced a new bill in December 2025, titled “Safeguarding Americans from Fraudulent and Experimental (SAFE) Drugs Act of 2025.” The bill proposes to restrict mass compounding of “essentially cop[ies]” of FDA-approved drugs and increase regulatory oversight on manufacturing and interstate distribution. Multiple lawsuits among the FDA, compounders, and pharmaceutical companies are ongoing, as well.

6. One trial or two? A key regulatory question emerges at FDA after some riffing

In an article with STAT News by Lizzy Lawrence on December 4, “FDA to lower number of trials required for approval of drugs, other medical products,” FDA Commissioner Dr. Marty Makary teased that the FDA would move toward a single-trial requirement for the approval of “most” drugs and certain medical products. He asserted that a single, well-designed trial can provide sufficient statistical power, although two trials may still be required in select cases. FDA expects to finalize the new policy within three to six months. This change would represent a significant deviation from more than six decades of regulatory precedent.

• While there are concerns that this change would weaken the regulatory benchmarks that evaluate drugs’ safety and efficacy, we imagine the new requirement could be applicable for certain oncology drugs, which are already reviewed on an expedited timeline, or more limited specialty drugs for rare diseases.

Within diabetes, we would be surprised to see the one-trial requirement implemented to all new drugs. Since 2008, when observational studies began to find that antihyperglycemic thiazolidinedione Avandia (rosiglitazone) may be associated with increased risk of heart attack and stroke, the FDA has required new diabetes drugs to undergo cardiovascular outcomes trial to demonstrate long-term safety. This regulatory requirement, in fact, led to the discovery that SGLT-2 inhibitors. Moreover, given the chronic and heterogeneous nature of the disease, long-term studies in diverse populations are valuable. For this reason, while trials could get bigger in number of participants tested, we would be very surprised if the double-trial requirement would simply disappear in more complex and chronic illnesses. Nonetheless, we wonder if the one-trial requirement could be applicable for drugs like a sixth-to-market SGLT-2 inhibitors or even classes like incretins that may be submitted in different combinations (GLP-1/GIP/glucagon, etc). We look forward to more detailed guidance from the FDA next year!

Top Five Most Read Closer Look Reports in Big Picture

1. ADA publishes 2026 Standards of Care – December 8, 2025 – Read on for the most important changes, ranging from CGM for non-insulin T2D, AID for insulin-using T2D, MASH, and expanded therapeutic options for glycemic targets
2. Blue Circle Health announces expansion of virtual T1D program to five additional states, for a total of 16 states with access to the platform – October 24, 2025 – Massachusetts, Connecticut, Pennsylvania, Virginia, and Kentucky will gain access to Blue Circle health, joining 11 states in the eastern US plus Iowa and Missouri
3. Most-Favored-Nation Pricing expands to offer GLP-1 RAs at $245/month through Medicare and Medicaid plus significant discounts through TrumpRx – November 6, 2025 – Federal government strikes deal with Novo Nordisk and Lilly to offer discounts for GLP-1 RAs and other therapeutics, highlighting cardiovascular and glycemic benefits
4. Novo Nordisk appoints Mr. Maziar Mike Doustdar as new President and CEO; Mr. Marcus Lang as new CSO; lowers 2025 guidance significantly due to ongoing challenges in the US – July 29, 2025 – Sales growth now expected at 8-14%, down from 13-21% due to compounding business, competition, and limited market expansion
5. Breakthrough T1D releases inaugural “State of T1D” report showing rising prevalence, widening demographic shifts, and technology access gaps – November 14, 2025 – Report compiles updated prevalence, demographic trends, and research milestones; aims to counter misinformation and elevate public awareness of T1D

Most Unexpected News/Biggest Surprises

1. CMS announces negotiated prices for 15 drugs in the second round of Medicare Drug Price Negotiation Program, including semaglutide
2. In unresolved dispute between Novo Nordisk BOD and the Novo Nordisk Foundation, Chairman of the Board Mr. Helge Lund exits, along with a majority (seven of 12) of board members
3. CMS announces next 15 drugs included in the second phase of Medicare Drug Price Negotiation program, including six diabetes-related medications
4. Most-Favored-Nation Pricing expands to nine additional pharmaceutical companies, including those focused on diabetes treatment
5. ICER publishes report on “fair” drug pricing, including T2D and obesity treatments
6. Novo Nordisk submits unsolicited ~$9 billion bid to acquire Metsera; offer may trigger “Superior Company Proposal” notice in Pfizer’s existing acquisition agreement
7. FDA establishes “green list” to regulate imports of GLP-1 RA active pharmaceutical ingredients and ensure safe treatment distribution – ten firms found to be non-compliant
8. Novo Nordisk terminates recent partnership with Hims & Hers for Wegovy (semaglutide), citing safety concerns

Notable Interviews in 2025

Diabetes Technology

• Interview with Glooko’s leadership team on its acquisition of Monarch Medical and the integration of inpatient insulin dosing algorithm EndoTool - On the Monarch Medical acquisition, CGM integration and care transition, EndoTool’s role in primary care and population health management, raising integration awareness among HCPs, and upcoming eCQM reporting requirements - (November 11, 2025)
• Interview with Biolinq CEO Mr. Rich Yang on Biolinq Shine, a patch-based CGM, and its FDA De Novo classification - On FDA’s GRM category creation, Biolinq Shine’s indication, intradermal and semiconductor design with LED-screen dual display, access strategy, and multi-analyte platform roadmap - (November 14, 2025)
• Interview with Sequel’s leadership team on twiist’s ongoing US launch, key differentiators, and future expansion into T2D - Discussion touches on phased US rollout for twiist, its key differentiators, and strategy to expand AID access and indications for T2D - (September 11, 2025)
• Interview with Tandem Diabetes Care’s President and CEO Mr. John Sheridan and EVP and Chief Administrative Officer Ms. Susan Morrison - Discussion included extended-wear infusion sets, pharmacy distribution channel, and benefits of AID - (September 11, 2025)
• Interview with Dexcom President & COO Mr. Jake Leach on strategic vision, innovation pipeline, and global expansion - Discussion covered 15-day sensor, adhesive innovation, Oura partnership, and Dexcom’s vision beyond diabetes - (August 11, 2025)
• Interview with Medtronic’s Ms. Que Dallara, Dr. Bob Vigersky, and Ms. Kate Cronin on MiniMed’s spinoff from Medtronic, Abbott partnership, 800-series pump, and InPen use - Discussion identifies touches on the upcoming split of MiniMed from Medtronic Diabetes; potential of 800-series pump and InPen - (August 4, 2025)
• Interview with Medtronic’s Dr. Bob Vigersky and Dr. Jen McVean on expanding MiniMed 780G adoption across diverse populations - Leadership muses on MiniMed 780G in expanded populations, including pregnancy and T2D, and promotes early AID adoption, women’s health - (June 25, 2025)
• Interview with pain specialist Dr. Krishnan Chakravarthy and Medtronic Inceptiv spinal cord stimulator (SCS) user, Mr. Scott Kasoff, explores the role of Inceptiv in managing diabetic painful neuropathy - Pain clinician Dr. Chakravarthy and DPN patient Mr. Kasoff provide insights on Inceptiv, Medtronic’s “closed-loop” SCS therapy for DPN, and the importance of patient and provider education - (July 3, 2025)
• Interview with Abbott’s EVP of Diabetes Mr. Chris Scoggins on Abbott’s initiatives, pipelines, and what’s to come - Discussion touched on upcoming dual glucose-ketone sensor; Above the Bias campaign and lasting impact on stigma; goal of empowering people with diabetes - (June 22, 2025)
• Interview with Insulet’s new CEO Ms. Ashley McEvoy, CMO Dr. Trang Ly, COO Mr. Eric Benjamin, and others on T2D adoption, international expansion, and progress toward fully closed-loop - (June 23, 2025)
• Interview with Abbott’s VP of North America Commercial Operations for Diabetes Care, Dr. Badia Boudaiffa, on the launch of the new Libre app in the US - New universal platform will allow for quicker application updates; ability to customize alarm settings; real-time FreeStyle Libre 2 data streaming launched - (April 15, 2025)
• Interview with Dexcom’s CEO Mr. Kevin Sayer on the launch of Stelo, T2D coverage, upcoming G8, and future of multi-analyte sensors - Dynamic discussion explores product strategy and additional populations who could benefit from CGM - (March 17, 2025)

Diabetes Therapy

• Interview with the T1D Fund’s new CEO Ms. Elizabeth Mily on her appointment and priorities for the Fund’s next chapter – The T1D Fund’s new CEO shares her personal motivations for joining the Fund, her vision for its future, and her goals to expand and strengthen partnerships to accelerate research and development toward finding a T1D cure – (March 4, 2025)
• Interview with Sernova’s CEO Mr. Jonathan Rigby on trial updates for Cell Pouch and visions for T1D cure(s) – Mr. Rigby shares his personal journey with T1D, trial updates for the Cell Pouch Bio-hybrid Organ, and insights on Sernova’s ongoing partnership with Evotec – (March 31, 2025)
• The challenges and opportunities for T1D autoantibody screening: A discussion with top Sanofi leaders, with significant food for thought – Sanofi’s Ms. April Kelly and Mr. John Strayer on raising awareness on T1D screening among PCPs, pediatricians, patients, and immediate family members of those with T1D – (May 20, 2025)
• Interview with Lexicon CMO Dr. Craig Granowitz and Head of External Affairs Dr. Alina Cocuzza on pipeline, FDA engagement, and Inpefa (sotagliflozin) differentiation strategy  – How Lexicon is navigating FDA dialogue and positioning sotagliflozin for broader impact – (September 25, 2025)

Big Picture

• Interview with head of Roche and Genentech’s new Boston Innovation Center, Dr. Manu Chakravarthy – Discussion explores how the Cardiovascular, Renal, and Metabolism hub will facilitate further expansion in research on AI/ML innovation and several of Roche’s diabetes and obesity candidates – (May 7, 2025)
• Interview with Team Novo Nordisk CEO Mr. Phil Southerland on the cycling team’s contract renewal with Novo Nordisk – Five-year extension of sponsorship and reducing stigma – (December 1, 2025)

2025 Resource Hubs for Scientific Conferences Attended by Close Concerns

Conference Resource Hubs continued to be our centralized one-stop-shops for all conference happenings in 2025. See below for all our Resource Guides covering conferences and meetings that took place in 2025 in order of occurrence.

1. Consumer Electronic Show- January 7-9, 2025
2. Changing the Course in T1D – January 13-14, 2025
3. JP Morgan Healthcare Conference - January 13-15
4. ADA Clinical Update Course- January 31-February 2
5. “Above the Bias” Launch – February 4, 2025
6. Diabetes UK (DUK)- February 26-28
7. nPOD 17^th Annual Scientific Meeting - March 2-5
8. 18^th Annual Conference on Advanced Technologies & Treatments for Diabetes (ATTD)- March 19-22
9. Annual American College of Cardiology (ACC) Conference - March 29-31
10. International Diabetes Federation (IDF) World Diabetes Congress - April 8-10
11. National Minority Quality Forum (NMQF) - April 28-29
12. European Association for the Study of the Liver (EASL) Congress 2025 - May 7-10
13. European Congress on Obesity (ECO) - May 11-14
14. American Association of Clinical Endocrinology (AACE) - May 15-17
15. DHNY Obesity+Health – May 20, 2025
16. embecta Analyst & Investor Day – May 22, 2025
17. Heart in Diabetes- June 6-8
18. ADA 85^th Scientific Sessions - June 20-23
19. Friends For Life- July 9-11, 2025
20. ENDO - July 12-15, 2025
21. ATDC - July 23-27, 2025
22. MDUFA VI Public Meeting – August 4, 2025
23. ADCES - August 8-11, 2025
24. ESC - August 29-September 1, 2025
25. EASD - September 15-19, 2025
26. Roche 2025 Pharma Day – September 22, 2025
27. HFSA - September 26-29, 2025
28. Rock Health Summit- September 30, 2025
29. Joslin International Symposium - October 7-9, 2025
30. CEU - October 23-25, 2025
31. CMHC - October 23-26, 2025
32. Breakthrough T1D Mission Summit - October 25-27, 2025
33. DTM - October 28-30, 2025
34. MTMVI Workshop - November 4, 2025
35. ObesityWeek - November 4-7, 2025
36. ISPAD - November 5-8, 2025
37. AHA - November 7-10, 2025
38. The Liver Meeting- November 8-11, 2025
39. Rachmiel Levine-Arthur Riggs Symposium - November 14-18, 2025
40. Insulet Investor Day – November 20, 2025
41. Cardiovascular, Kidney, and Metabolic Outcomes CVOT Summit - November 23, 2025
42. WCIRDC - December 3-6, 2025
43. ATTD-Asia - December 9-11, 2025
44. Zealand Pharma Capital Markets Day – December 11, 2025
45. ADCES Diabetes Technology Conference - December 12-13, 2025

Literature Shared in 2025

In 2025, we shared a total of 225 pieces of literature in our Closer Look newsletter. Breaking that number down, we shared 18 in January, 15 in February, 15 in March, 16 in April, 16 in May, 21 in June, 24 in July, 23 in August, 20 in September, 24 in October, 16 in November, and 17 in December. Put another way, that’s 21% in the first quarter, 23.5% in the second quarter, 30% in the third quarter, and 25.5% so far in the fourth quarter.

December 2025

November 2025

October 2025

September 2025

August 2025

July 2025

June 2025

May 2025

April 2025

March 2025

February 2025

January 2025

--by Riya Chatterjee, Kayla Mathieu, Elizabeth Rose, Jeremy Alkire, Kat Moon, Esther Min, Monica Oxenreiter, and Kelly Close