FDA Approves First Oral GLP-1 for Weight Management

The FDA has approved the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for chronic weight management, marking a major shift in the treatment landscape for obesity and overweight. The semaglutide (Wegovy; Novo Nordisk) pill offers patients a noninjectable alternative with weight loss efficacy comparable to the original injectable formulation, expanding access to GLP-1 therapy for millions of US adults living with obesity or overweight with at least 1 weight-related comorbidity.¹

“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,” said Mike Doustdar, president and CEO of Novo Nordisk. “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. No other current oral GLP-1 treatment can match the weight loss delivered by the Wegovy pill, and we are very excited for what this will mean for patients in the US.”¹

Clinical Evidence Supporting Approval

The FDA’s decision was supported by findings from the OASIS 4 trial (NCT05564117), including results published in The New England Journal of Medicine.^1,2 In OASIS 4, adults with overweight or obesity receiving oral semaglutide 25 mg once daily experienced substantial and clinically meaningful weight reduction compared with placebo, alongside improvements in cardiometabolic risk factors.³ The estimated mean change in body weight from baseline to week 64 was −13.6% in the oral semaglutide group and −2.2% in the placebo group.³

Importantly, the trial demonstrated that oral semaglutide could overcome historic bioavailability challenges associated with peptide-based medications. Using a coformulated absorption enhancer, the oral formulation enabled consistent systemic exposure sufficient to drive weight loss outcomes previously achievable only through injection.³ These results address longstanding adherence barriers for patients who are reluctant to initiate or continue injectable therapies.

Safety and Tolerability Considerations

The safety profile of the semaglutide pill was consistent with that of other GLP-1 receptor agonists. The most commonly reported adverse events were gastrointestinal, including nausea, vomiting, diarrhea, and constipation, particularly during dose escalation.³ These effects were generally transient and manageable with appropriate titration and counseling. As with injectable semaglutide, warnings related to pancreatitis, gallbladder disease, and risk of thyroid C-cell tumors remain relevant and are included in the prescribing information.¹

Pharmacists will play a critical role in educating patients on dose titration schedules, administration requirements, and management of gastrointestinal adverse effects to optimize adherence and outcomes.

Additionally, the oral formulation may reshape payer dynamics and prescribing patterns within the increasingly competitive obesity treatment market. Analysts note that the FDA approval contributed to a significant rise in Novo Nordisk’s stock price, reflecting strong investor confidence in the commercial potential of oral GLP-1 therapies.⁴ As demand for obesity treatments continues to grow, pharmacists will need to stay informed about coverage criteria, prior authorization requirements, and evolving clinical guidelines.

Conclusion

The approval of the semaglutide pill highlights the rapid evolution of obesity pharmacotherapy and the expanding role of GLP-1 receptor agonists beyond injectable delivery. Ongoing clinical studies continue to evaluate long-term outcomes and broader applications of oral semaglutide in metabolic disease management.³ For pharmacists, this milestone reinforces the importance of staying at the forefront of evidence-based obesity care and supporting patients through individualized, accessible treatment options.

REFERENCES

1. Novo Nordisk A/S: Wegovy® pill approved in the US as first oral GLP-1 for weight management. Novo Nordisk. Published December 22, 2025. Accessed December 23, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916472

2. Research Study Looking at How Well Semaglutide Tablets Taken Once Daily Work in People Who Have a Body Weight Above the Healthy Range (OASIS 4). NCT05564117. Clinicaltrials.gov. Updated December 4, 2025. Accessed December 23, 2025. https://clinicaltrials.gov/study/NCT05564117

3. Wharton S, Lingvay I, Bogdanski P, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. New England Journal of Medicine. 2025;393(11):1077-1087. doi:10.1056/nejmoa2500969

4. Carson E. Novo Nordisk Jumps As FDA OKs Wegovy Pill As First-Ever Oral GLP-1 Weight Loss Drug. Investors.com. Published December 23, 2025. Accessed December 23, 2025. https://www.investors.com/news/technology/novo-nordisk-stock-jumps-fda-oks-wegovy-pill-first-oral-glp-1-weight-loss-drug/