Oral Wegovy receives FDA approval for weight loss  – 

Based on OASIS-4 trial, in which oral semaglutide 25 mg conferred up to 14% weight loss (vs. 2%) at 64 weeks, and SELECT CVOT; launch expected in early January 2026

Novo Nordisk announced today that the FDA approved its Wegovy pill (once-daily oral semaglutide 25 mg) 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 higher “maintenance” dose should enable significantly more weight loss for people who are open to taking it chronically.

The approval is based on phase 3 OASIS-4 (n=307) and SELECT trials (n=17,604). In OASIS 4, as presented at ObesityWeek 2024, oral semaglutide 25 mg conferred up to 14% weight loss compared to 2% with placebo at 64 weeks, from a baseline of 106 kg (23 lbs). In the SELECT trial, injectable semaglutide 2.4 mg reduced major adverse CV events (MACE) risk by 20% at Week 104 in people with obesity or who were overweight, but without diabetes.

It was very striking to see both Novo Nordisk’s US website as well as the global website with this news on the front page. Even more striking, Novo Nordisk plans to launch Wegovy pills in the US in early January 2026 – in just a couple of weeks! Outside the US, the company also submitted oral semaglutide in the EU in 3Q24 for weight management based on the phase 3b OASIS-1  and PIONEER PLUS trials.

OASIS program demonstrated significant weight loss in people with overweight or obesity

The approval of the Wegovy pill reflected results from the phase 3 OASIS-4 trial (n=307) presented at The Obesity Society in 2024 that evaluated oral semaglutide 25 mg in people with obesity or overweight without diabetes. Oral semaglutide 25 mg significantly lowered body weight by just under 14% from a baseline of 106 kg (233 lbs) vs. 2.2% in placebo at 64 weeks. Categorically, half of the participants in the semaglutide group achieved ≥15% weight loss vs. 6% in the placebo group, and 30% achieved ≥20% weight loss vs. 3% in the placebo group. A1c levels also dropped significantly by 0.29 percentage points vs. 0.06 in the placebo group (baseline of 5.7%), with 71% of participants with prediabetes at baseline reverting to normoglycemia, compared to 33% in the placebo group. We view these last results as especially striking as they may prompt the Wegovy pill to be considered for type 2 diabetes delay or prevention (this is speculation by Close Concerns). It was fantastic to see what could happen at higher doses of Wegovy vs. Rybelsus, which isn’t available at this dose. We also loved seeing that the starting dose of the Wegovy pill was much lower than Rybelsus (1.5 mg vs. 3.0 mg).

The safety profile of oral semaglutide 25 mg was consistent with that of injectable semaglutide and other incretin-based therapies. 74% of participants taking semaglutide experienced a GI-related adverse event (e.g., nausea, vomiting, or constipation) compared to 42% in placebo.

The OASIS-4 trial is part of the larger OASIS program, which investigated oral semaglutide 25 mg and 50 mg.

  • The OASIS-1 trial (n= 667) evaluated oral semaglutide as an adjunct to lifestyle intervention in people with obesity or overweight with one weight-related comorbidity, without T2D. Semaglutide 50 mg conferred 16% weight loss at 68 weeks from a baseline of 104 kg (230 lbs) vs. 2% weight loss with placebo from a baseline of 106 kg (234 lbs) in the trial product estimand. On safety, 80% of the oral semaglutide group experienced GI-related events, compared to 46% in the placebo group.
  • The OASIS-2 trial (n=2o1) assessed oral semaglutide in East Asian individuals with overweight or obesity with and without diabetes. On average, participants achieved 14% weight loss compared to 1% with placebo at 68 weeks.
  • The OASIS-3 trial (n=200) tested oral semaglutide in Chinese adults in the healthy weight range.

CV benefits from SELECT trial results extended from injectable to oral formulations

While oral semaglutide was not specifically studied in a CV outcomes trial in people with overweight or obesity, the FDA approved oral semaglutide for MACE risk reduction based on the landmark phase 3 SELECT trial (n=17,604). In the trial, injectable semaglutide conferred a 20% MACE reduction in people with overweight or obesity.

Similar CV benefits are found in the secondary endpoints of the OASIS-4 trial. C-reactive protein, a biomarker for inflammation, decreased significantly by 46% vs. 4% in placebo from a baseline of 3.7 mg/L. Systolic and diastolic blood pressure reductions were numerically greater in the semaglutide group, although they were not statistically significant.

Separately, in the phase 3b SOUL trial (n=9,650), Rybelsus (oral semaglutide for T2D) demonstrated a 14% reduction in MACE compared to placebo. It was approved in both the US and EU for reducing MACE in adults with T2D and high cardiovascular risk.

Oral GLP-1 RAs on the races: Orforglipron, AZD 5004, VK2735, and more in the pipeline

Companies continue to advance oral incretin-based therapies for weight management to patients who may be needle-averse or otherwise prefer oral formulations. Lilly’s oral GLP-1 RA orforglipron 36 mg is the most advanced candidate in the pipeline. In the phase 3 ATTAIN-1 trial (n=3,127), it demonstrated 12% weight loss in people with obesity at Week 72 with a safety and tolerability profile consistent with other incretin-based therapies.

In earlier stages, Viking’s oral VK2735 (dual GLP-1/GIP RA) demonstrated 8.3% weight loss across treatment groups at 13 weeks in a phase 2 VENTURE-Oral dosing trial (n=280). In 3Q25, Viking shared plans to meet with regulatory agencies in 4Q25. AstraZeneca is also advancing oral GLP-1 RA AZD 5004, which is currently evaluated in two phase 2b trials for AZD5004 (VISTA for obesity and SOLSTICE for T2D).

Pfizer’s danuglipron (oral GLP-1 RA), which had shown up to 13% weight loss and discontinuation rate of over 50% in a phase 2b trial (n=628), was discontinued in April 2025 due to a case of potential drug-induced liver injury and high rates of GI-related adverse events in earlier trials.

Wegovy pill to be priced at $150/month on TrumpRx based on the Most Favored Nation policy

In November 2025, the White House announced the expansion of Most-Favored-Nation (MFN) pricing to offer GLP-1 RAs, such as Ozempic, Wegovy, Mounjaro, and Zepbound, at a significant discount of $245 per month and a patient’s co-pay of $50 per month. While not approved at the time of announcement, oral GLP-1 RAs were also included in this deal. Wegovy pills and orforglipron will be priced at $150 per month and $346 per month, respectively, on TrumpRx direct-to-consumer platform.

Moreover, in the same month, the Centers for Medicare and Medicaid Services (CMS) announced negotiated prices for 15 drugs included in the Medicare Drug Price Negotiation Program (MDPNP). Effective January 1, 2027, semaglutide products – Ozempic, Wegovy, and Rybelsus – will be 71% lower than the current list prices, at $277, $386, and $277 per month, respectively. Given that the Wegovy pill is also a semaglutide product, we are curious if it will be included in the MDPNP with a similarly lower cost.

Close Concerns’ Questions

  1. How did the FDA decide to extend the SELECT results to the oral formulation of semaglutide?
  2. How will the availability of oral formulation affect the uptake of incretin-based therapies?
  3. How might oral semaglutide compare to orforglipron in people with overweight or obesity? As background, in the phase 3 ACHIEVE-3 trial, orforglipron demonstrated a 74% relative improvement in weight loss (9.2%) compared to oral semaglutide (5.3%) in people with inadequately managed T2D.
  4. Might Novo Nordisk pursue an even higher dose of oral semaglutide, such as 50 mg?
  5. Will Novo Nordisk evaluate oral semaglutide in people with T1D?
  6. Will Novo Nordisk pursue a T2D delay or prevention in a subgroup of very high-risk individuals?

--by Kat Moon, Esther Min, and Kelly Close

Oral Wegovy receives FDA approval for weight loss -
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