FDA Sets Action Date for Oral Wegovy for Weight Loss

The FDA has accepted Novo Nordisk’s new drug application (NDA) for a once-daily, 25 mg oral formulation of Wegovy (semaglutide) for adults living with obesity and to reduce the risk of major adverse cardiovascular events (MACE) in adults with overweight or obesity and established cardiovascular disease. If approved, Wegovy would become the first oral formulation of a GLP-1 indicated for chronic weight management.

A decision is expected in the fourth quarter of 2025.

The FDA application is based on results from OASIS 4, a phase 3 trial evaluating once-daily oral semaglutide 25 mg compared with placebo. The trial enrolled 307 adults who were obese or who were overweight. Patients with diabetes were excluded. The trial included a 64-week treatment period including a 12-week dose escalation and a 7-week off-treatment follow-up period.

The trial found that once-daily oral semaglutide 25 mg reduced body weight, increased physical function, and improved metabolic health in adults with overweight/obesity, with comparable efficacy to semaglutide 50 mg in the OASIS 1 trial. A greater proportion of participants achieved weight loss in the semaglutide group compared with placebo.

Additionally, significant improvements in cardiometabolic risk factors were also observed with semaglutide vs placebo. Adverse events leading to treatment discontinuation were comparable between groups.

Data from the OASIS 4 trial were presented in November 2024 at ObesityWeek2024.

OASIS is a phase 3 clinical development program with once-daily oral semaglutide 25 mg and 50 mg in adults with obesity. The program currently consists of four trials, having enrolled approximately 1,300 adults with obesity or overweight with one or more comorbidities.

This news comes after results of several other oral GLP-1 therapies were released. Last week, Lilly reported positive topline phase 3 results from ACHIEVE-1 for orforglipron in adults with type 2 diabetes. It also reduced weight by an average of 16.0 lbs (7.9%) at the highest dose in a key secondary endpoint.

The overall safety and tolerability profile of orforglipron in ACHIEVE-1 was consistent with injectable GLP-1 therapies

Related: Liver Injury Ends Development of Pfizer’s Oral GLP-1 for Obesity

But Pfizer stopped clinical development of its once-daily oral GLP-1 candidate to treat obesity. Danuglipron was being studied for adults with obesity and without type 2 diabetes.

Company executives said that the overall frequency of elevated liver enzymes across the more than 1,400 participants in the clinical development program of danuglipron was in line with approved drugs in the class. But in one of the dose optimization studies, an asymptomatic patient experienced potential drug-induced liver injury, which resolved after discontinuation of danuglipron.

Novo Nordisk already markets an oral semaglutide product. Rybelsus is approved to treat type 2 diabetes. It is available in both 7 mg and 14 mg and has a list price of $997.58 per package. People with commercial insurance may pay as little as $10 for a one-, two-, or three-month prescription.

In March 2025, Novo Nordisk reported the results of the SOUL trial, which assessed Rybelsus 14 mg to lower cardiovascular risk in adults with type 2 diabetes. This trial found that Rybelsus reduced the risk of major adverse cardiovascular events (MACE) by 14% compared with placebo in adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). These data were presented at the American College of Cardiology’s Annual Scientific Session and Expo.

Novo Nordisk has submitted a supplemental application to the FDA for Rybelsus 14 mg for this indication. A regulatory decision is anticipated in 2025.