FDA Approves Oral Wegovy: First GLP-1 Pill for Weight Management

Background and Clinical Context

Semaglutide, a GLP-1 receptor agonist, is well established for the treatment of type 2 diabetes and obesity. Injectable formulations have demonstrated significant glycemic and weight-loss benefits, while the approval of oral semaglutide (Rybelsus) for diabetes expanded options for patients who prefer non-injectable therapy. The development of oral semaglutide (Wegovy) for weight management further reduces barriers related to injections and supports long-term obesity care.

Regulatory Status and Indications

On December 22, 2025, the FDA approved oral semaglutide (Wegovy) for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity, including reduction of major adverse cardiovascular events in adults with established cardiovascular disease and obesity or overweight.

Although both oral Wegovy and Rybelsus contain semaglutide, they differ in indication and dose. Rybelsus is approved for type 2 diabetes at doses up to 14 mg daily, whereas oral Wegovy is approved for weight management at a maintenance dose of 25 mg daily.

Pharmacology, Formulation, and Administration

Semaglutide enhances glucose-dependent insulin secretion, delays gastric emptying, and suppresses appetite. Oral delivery is limited by gastrointestinal degradation and poor intestinal absorption, necessitating absorption enhancers and higher doses than injectable formulations.

Oral Wegovy is initiated at 1.5 mg once daily and titrated over 90 days to reach the maintenance dose to reduce gastrointestinal adverse effects. Tablets must be taken on an empty stomach with no more than 4 ounces of water, at least 30 minutes before food, beverages, or other oral medications, as improper administration reduces efficacy.

Clinical Efficacy and Safety

In the OASIS 4 trial, adults without diabetes receiving oral Wegovy achieved a mean weight loss of 13.6% over 64 weeks, compared with 2.2% with placebo. Weight-loss outcomes were comparable to injectable semaglutide.

The most common adverse effects are gastrointestinal, including nausea, diarrhea, vomiting, and constipation. These effects are transient and can be managed with gradual dose escalation and patient counseling.

Transitioning Between Formulations

Oral and injectable semaglutide are not bioequivalent, so doses are not directly interchangeable. According to FDA prescribing information, patients taking Wegovy 2.4 mg injection for weight management may switch to oral Wegovy 25 mg tablets one week after discontinuing the injection, initiating the oral formulation at 25 mg once daily.

Practice Takeaways

Oral Wegovy expands GLP-1 treatment options for obesity by providing an effective non-injectable alternative. Pharmacists play a key role in optimizing outcomes through patient education, adherence support, adverse effect monitoring, and guidance during formulation transitions. Clear counseling on administration and switching is essential to maximize benefit.

Sources

• Wharton S, Lingvay I, Bogdanski P, Duque do Vale R, Jacob S, Karlsson T, Shaji C, Rubino D, Garvey WT; for the 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. Published September 17, 2025.
• Novo Nordisk Inc. WEGOVY® (semaglutide) tablets, for oral use: Highlights of Prescribing Information. U.S. Food and Drug Administration; Revised December 2025. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218316Orig1s000lbl.pdf.
• Novo Nordisk Inc. Wegovy® pill, the first and only oral GLP-1 for weight loss in adults, now broadly available across America. Plainsboro, NJ: U.S. Communications, Novo Nordisk; December 2025. Available from: https://ml-eu.globenewswire.com/Resource/Download/5daa1d12-c639-4f02-b025-2fdae156fc38.