Oral Semaglutide 50 mg Reduces Bodyweight in Adults Without Type 2 Diabetes

Oral semaglutide 50 mg decreases bodyweight in adults with overweight or obesity without type 2 diabetes, according to a double-blind, placebo-controlled study published in The Lancet.

The study authors included 667 individuals (mean age, 50 years; 73% women) with a body mass index (BMI) of at least 30 kg/m² or at least 27 kg/m² with bodyweight-related complications and comorbidities without type 2 diabetes in the multicentric, phase 3 clinical trial conducted between September 13 and November 22, 2021. Study participants underwent random assignment to oral semaglutide 50 mg (n=334) or placebo (n=333) treatment once daily for 68 weeks with lifestyle intervention. Coprimary endpoints were percentage change in bodyweight and whether participants reached a 5% bodyweight reduction or more at 68 weeks. Secondary endpoints were whether the study individuals achieved at least 10%, 15%, and 20% bodyweight reduction and participant-reported physical function outcome changes from baseline to week 68. 

The average change in bodyweight from baseline was −15.1% for the oral semaglutide 50 mg group compared with −2.4% for the placebo group (mean difference, −12.7%; 95% CI, −14.2 to −11.3; P <.0001). Participants treated with oral semaglutide 50 mg achieved more significant reductions in bodyweight, with 85% meeting the 5% bodyweight reduction efficacy endpoint compared with 26% of individuals treated with placebo (odds ratio [OR], 12.6; 95% CI, 8.5-18.7; P <.0001). More individuals treated with oral semaglutide achieved a 10% (69% vs 12%), 15% (54% vs 6%) or 20% (34% vs 3%) bodyweight reduction compared with control group participants.

Overall, 92% of participants in the oral semaglutide 50 mg group experienced adverse events, compared with 86% in the placebo group.  Most adverse events were mild to moderate and gastrointestinal in nature (oral semaglutide: 80% vs placebo: 46%).

“Oral semaglutide 50 mg taken once per day, the first oral GLP-1 receptor agonist to be investigated for the treatment of obesity in adults with overweight or obesity, was shown to induce substantial, clinically meaningful bodyweight reductions as an adjunct to diet and physical activity,” according to the study authors.

Study limitations include an overrepresentation of women and individuals of White race, and a failure to monitor treatment adherence.

Disclosure: This research was supported by Novo Nordisk. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.