The results of OASIS 4 phase 3 trial, which demonstrated the safety and efficacy of once-daily oral semaglutide 25 mg for weight loss in adults with overweight or obesity, are now published.

The results were first presented late last year during Obesity Week 2024 and reported by Medscape Medical News at that time.

The full trial results were published online on September 17 in The New England Journal of Medicine.

The US FDA is set to decide on Novo Nordisk’s new drug application for oral semaglutide 25 mg for chronic weight management in adults living with obesity or overweight later this year. If approved, it would become the first oral formulation of a GLP-1 indicated for chronic weight management.

The approval of oral semaglutide “should and will change and enhance the practice of obesity medicine. This medication should be easier to make and distribute than injectables that require refrigeration and a cold-chain system,” OASIS 4 investigator Sean Wharton, MD, with the University of Toronto, Toronto, Ontario, Canada, and the Wharton Weight Management Clinic, Burlington, Ontario, told Medscape Medical News.

In OASIS 4, the efficacy of oral semaglutide 25 mg was “quite good with tolerable adverse effects in keeping with GLP-1s,” Wharton added.

OASIS 4 Refresher

Semaglutide is currently approved in the US for weight management as a once-weekly subcutaneous injection. In a recent trial, a 50-mg dose of once-daily oral semaglutide resulted in significantly greater weight loss than placebo. However, the efficacy and safety of lower doses of oral semaglutide were unclear.

To fill this gap, OASIS 4 randomly assigned 307 adults with diabetes with BMI ≥ 30 or with BMI ≥ 27 and at least one obesity-related complication to receive once-daily oral semaglutide 25 mg or matching placebo, along with lifestyle intervention.

Among patients who adhered to treatment, those receiving oral semaglutide 25 mg achieved average weight loss of 16.6% compared to 2.7% in those receiving placebo at 64 weeks (P < .0001).

Regardless of strict adherence to treatment, patients receiving oral semaglutide still achieved an average weight loss of 13.6% compared with 2.2% in those receiving placebo (P < .001).

Patients in the oral semaglutide group were also significantly more likely to have a reduction of at least 5% in body weight than those in the placebo group.

From baseline to week 64, 79.2% vs 31.1% of those in the semaglutide vs placebo group lost ≥ 5% of body weight, 63.0% vs 14.4% lost ≥ 10%; 50.0% vs 5.6% lost ≥ 15%; and 29.7% vs 3.3% lost ≥ 20%. All differences were statistically significant at P < .0001.

Weight loss results with oral semaglutide 25 mg were similar to that achieved in previous trials involving oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg.

Oral semaglutide 25 mg was also associated with improved physical function and substantial reductions in cardiometabolic risk factors including BMI, waist circumference, levels of glycated hemoglobin, fasting plasma glucose, fasting serum insulin, lipids (very low-density lipoprotein and triglycerides), and C-reactive protein.

Notably, most patients with prediabetes at baseline had normoglycemia at the end of semaglutide treatment, the researchers reported.

Overall adverse events occurred in 93.1% of patients receiving oral semaglutide and in 85.3% of those receiving placebo, and gastrointestinal adverse events occurred in 74.0% and 42.2% of patients, respectively. Most of the events were mild or moderate in severity and were resolved without a need for permanent discontinuation of the regimen, the researchers said.

Taken together, the results of OASIS 4 support oral semaglutide 25 mg as an efficacious option for obesity, they concluded.

Wharton told Medscape Medical News, this study is “going to change practice. If taking a pill is what you prefer, you will have the option.”

The OASIS 4 study was funded by Novo Nordisk. Disclosures for authors are available at nejm.org.