Oral Semaglutide Shows Promise for Weight Loss and Cardiometabolic Health

In the phase 3 OASIS 4 post hoc analysis, 25 mg of oral semaglutide (Wegovy in a pill) was associated with improvements in glucose control and cardiovascular (CV) risk factors across multiple categories of weight loss. Investigators presented the findings during ObesityWeek 2025, which took place in Atlanta, GA.¹

"Novo Nordisk has pioneered innovation in the obesity class for 25 years, and the oral semaglutide data at ObesityWeek reflect our drive to improve the lives of people living with obesity," Martin Holst Lange, chief scientific officer and executive vice president of Research & Development at Novo Nordisk, said in a news release. "The OASIS 4 results that we are sharing at this important meeting build on existing clinical trial evidence for oral semaglutide and extend findings beyond weight loss to suggested improvements in overall health."¹

What is Oral Semaglutide?

Oral semaglutide is a prescription medication approved to manage type 2 diabetes (T2D) in combination with diet and exercise. It also helps reduce the risk of heart attack, stroke, or death in patients with T2D who have a high CV risk. The drug is a glucagon-like peptide (GLP-1) receptor agonist that is available in tablet form.²

GLP-1s are typically recommended as add-on therapy after metformin for patients who need better glucose control, especially when promoting weight loss. These drugs traditionally require self-injection, but the introduction of oral semaglutide offers an alternative for patients who prefer to not use injectable medications.³

Currently, the 25 mg oral semaglutide, or Wegovy in a pill, is not yet approved by the FDA. The company noted that they submitted a new drug application for the once-daily pill version of Wegovy, and the FDA is expected to complete its review by the end of 2025. If approved, it would be the first oral GLP-1 medication available for weight loss.¹

Wegovy in a Pill Demonstrates Significant Reductions and Results

Data from the post hoc analysis from the OASIS 4 phase 3 trial found that adults with overweight or obesity who took once-daily oral semaglutide 25 mg experienced greater weight loss and improvements in glucose control and CV risk factors compared with placebo. The treatment significantly reduced HbA1c, fasting glucose, fasting insulin, C-reactive protein, and triglyceride levels.¹

"As recently published in The New England Journal of Medicine, the primary results from the OASIS 4 clinical trial demonstrated weight loss efficacy of investigational oral semaglutide 25 mg as a potential therapeutic option for people with obesity and overweight," Domenica Rubino, MD, trial investigator and director of the Washington Center for Weight Management and Research in Washington, DC, said in the news release.¹

Further results from a pooled analysis of the OASIS 4 and STRP trials found that semaglutide led to significant weight loss in women across all menopause stages. Over 64 weeks, premenopausal women lost an average of 18.2% of body weight, perimenopausal women lost 15%, and postmenopausal women lost 15.7%, with more than half of participants in each group achieving over 15% weight loss.¹

Another OASIS 4 analysis showed that participants with obesity and poor physical function at baseline experienced notable improvements. Overall, 77.3% of those taking 25 mg of oral semaglutide reported meaningful gains compared to 42.9% in the placebo group.¹

Adverse events with oral semaglutide were mild to moderate in severity. The most common reactions included nausea and vomiting, reinforcing the safety and tolerability profile of the drug.¹

"It's exciting to see these new results from the cardiometabolic post hoc analysis, which showed that while benefits were most pronounced in people who achieved greater than 15% weight loss, clear improvements in glycemic parameters and CV risk factors were observed in patients taking oral semaglutide 25 mg, regardless of how much weight was lost, based on the groups observed,” Rubino concluded.¹

REFERENCES

1. Novo Nordisk presents four new analyses on oral semaglutide 25 mg (Wegovy® in a pill*) at ObesityWeek® 2025, including demonstrated reductions in cardiovascular risk factors. Novo Nordisk. News release. November 5, 2025. Accessed November 5, 2025. https://www.prnewswire.com/news-releases/novo-nordisk-presents-four-new-analyses-on-oral-semaglutide-25-mg-wegovy-in-a-pill-at-obesityweek-2025-including-demonstrated-reductions-in-cardiovascular-risk-factors-302605339.html

2. Mayo Clinic. Semaglutide (oral route). News release. Accessed November 5, 2025. https://www.mayoclinic.org/drugs-supplements/semaglutide-oral-route/description/drg-20492085

3. Hughes S, Neumiller JJ. Oral Semaglutide. Clin Diabetes. 2020 Jan;38(1):109-111. doi: 10.2337/cd19-0079. PMID: 31975761; PMCID: PMC6969659.