FDA Approves Oral Semaglutide as First GLP-1 Pill for Weight Loss

The FDA has approved the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for weight loss and to reduce the risk of major adverse cardiovascular events (MACE).¹ Novo Nordisk plans to launch the once-daily oral semaglutide (Wegovy) 25 mg in the US in early January 2026.

The approval is based on results from the OASIS clinical trials and the SELECT trial. OASIS 4 showed a mean weight loss of 13.6% at 64 weeks.² The study evaluated the efficacy and safety of once-daily oral semaglutide with lifestyle counseling compared with placebo.

“The pill is here. With today's approval of the Wegovy pill, patients will have a convenient, once-daily pill that can help them lose as much weight as the original Wegovy injection,” Mike Doustdar, president and CEO of Novo Nordisk, said in a statement.¹ “As the first oral GLP-1 treatment for people living with overweight or obesity, the Wegovy pill provides patients with a new, convenient treatment option that can help patients start or continue their weight loss journey.”

Efficacy and Safety of Oral Semaglutide in the OASIS 4 Trial

The OASIS 4 trial enrolled 307 adults without diabetes who had obesity or overweight (body mass index [BMI] of ≥ 30 or ≥ 27 with at least 1 obesity-related complication) who received either oral semaglutide (n = 205) or placebo (n = 102). The coprimary end points were the percent change in body weight and a reduction of 5% or more in body weight at week 64.

Patients on oral semaglutide recorded a significantly greater mean change in body weight from baseline to week 64 compared with patients on placebo (–13.6% vs –2.2%; 95% CI, –13.9% to –9.0%; P < .001). The study also estimated the hypothetical trial-product estimand, which estimates treatment effect assuming patients adhere to the treatment as assigned, resulting in a mean change in body weight of –16.6% for oral semaglutide and 2.7% for placebo (95% CI, –16.5% to –11.2%).

Not only was the reduction in relative body weight similar across subgroups based on BMI at baseline, but there was also no evidence the effect varied by sex, race, or ethnic group.

Most adverse events (AEs)—experienced by 93.1% of patients on oral semaglutide and 85.3% of patients on placebo—were mostly mild or moderate and resulted in no permanent discontinuation of treatment. The most frequent AEs were gastrointestinal disorders (74.0% oral semaglutide and 42.2% placebo).

Oral Semaglutide for Weight Loss on the US Market

Novo Nordisk has indicated that it plans to launch the 25 mg oral semaglutide in the US in 2026.

Oral semaglutide was first approved in 2019 for type 2 diabetes, when it became the first oral GLP-1 approved by the FDA.³

Most recently, the FDA had expanded the indication for semaglutide tablets 7 and 14 mg to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes who are at an elevated risk.⁴ The indication also covered patients without a prior heart attack or stroke.

Oral GLP-1 Competition on the Horizon

The FDA decision gives oral semaglutide an edge in a competitive weight loss market with Eli Lilly having submitted its own oral GLP-1, orforglipron, to the FDA for review.^5,6 Orforglipron is an investigational, non-peptide, once-daily oral GLP-1 receptor agonist that can be taken without restrictions on food or water intake.

Topline results from the phase 3 ATTAIN-MAINTAIN trial showed orforglipron met the primary end point of superior percent maintenance of body weight reduction compared with placebo. In addition, patients who switched from semaglutide to orforglipron maintained their previously achieved weight loss. The change in body weight from baseline to 24 weeks for patients who switched from semaglutide to orforglipron was –0.1 kg vs 9.4 kg for placebo.⁶

“The oral option could improve long-term adherence by offering patients a non-injectable alternative with similar metabolic benefits,” W. Timothy Garvey, MD, professor in the University of Alabama at Birmingham (UAB) School of Health Professions and a lead for the oral semaglutide clinical trial site at UAB, said in a statement.⁷ “We need ways to keep patients on these medicines long term, and an effective oral preparation could help us do that.”

References

1. Novo Nordisk A/S: Wegovy pill approved in the US as first oral GLP-1 for weight management. News release. Novo Nordisk. December 22, 2025. Accessed December 22, 2025. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916472

2. Wharton S, Lingvay I, Bogdansi P, et al; OASIS 4 study group. Oral semaglutide at a dose of 25 mg in adults with overweight or obesity. N Engl J Med. 2025;393(11):1077-1087. doi:10.1056/NEJMoa2500969

3. Caffrey M. FDA approves Novo Nordisk’s oral semaglutide, first GLP-1 in pill form. AJMC^®. September 20, 2019. Accessed December 23, 2025. https://www.ajmc.com/view/fda-approves-novo-nordisks-oral-semaglutide-first-glp1-in-pill-form

4. Klein H. FDA expands semaglutide label to reduce cardiovascular risk in adults with type 2 diabetes. AJMC. October 20, 2025. Accessed December 23, 2025. https://www.ajmc.com/view/fda-expands-semaglutide-label-to-reduce-cardiovascular-risk-in-adults-with-type-2-diabetes

5. Jennings S. Phase 3 data support oral orforglipron for weight maintenance after GLP-1–based weight loss. Patient Care^®. December 19, 2025. Accessed December 22, 2025. https://www.patientcareonline.com/view/phase-3-data-support-oral-orforglipron-for-weight-maintenance-after-glp-1-based-weight-loss

6. Lilly's orforglipron helped people maintain weight loss after switching from injectable incretins to oral GLP-1 therapy in first-of-its-kind phase 3 trial. News release. Eli Lilly. December 18, 2025. Accessed December 23, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-orforglipron-helped-people-maintain-weight-loss-after

7. FDA approves oral version of weight-loss drug semaglutide, UAB researchers react. News release. University of Alabama at Birmingham. December 22, 2025. Accessed December 23, 2025. https://www.uab.edu/news/research-innovation/fda-approves-oral-version-of-weight-loss-drug-semaglutide-uab-researchers-react