Patients with overweight or obesity who received oral semaglutide 25 mg once daily lost more weight than those who received placebo at 64 weeks, according to findings from the phase 3 OASIS-4 trial. The mean weight reduction was 14% in the semaglutide group and 2% in the placebo group. Patients receiving semaglutide were more likely to achieve weight reductions of between 5% and 20%. Treatment was also associated with improvements in metabolic outcomes. 

The study was a double-blind, randomized, placebo-controlled trial conducted at 22 sites in Canada, Germany, Poland, and the United States. A total of 307 patients without diabetes were enrolled. Eligible patients were 18 years or older with a body-mass index of at least 30, or at least 27 with one or more obesity-related complications. Patients were randomized in a 2:1 ratio to receive semaglutide or placebo in addition to lifestyle interventions. Dosing began at 3 mg and was escalated to 25 mg over 12 weeks, then maintained through week 64.

Patients who received semaglutide had larger decreases in body-mass index, waist circumference, glycated hemoglobin, fasting plasma glucose, triglycerides, very-low-density lipoprotein cholesterol, insulin, and C-reactive protein. Among those with prediabetes at baseline, most achieved normoglycemia by week 64. Physical function improved more in the semaglutide group, with more than half reporting clinically meaningful gains on the IWQOL-Lite-CT Physical Function scale.

Adverse events were consistent with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) drug class. Gastrointestinal events were reported in 74% of patients in the semaglutide group compared with 42% in the placebo group. Nausea and vomiting were the most frequent symptoms, generally mild to moderate and transient. Serious adverse events occurred in 4% of patients in the semaglutide group and 9% of those in the placebo group. Discontinuation due to adverse events was similar between the groups. No deaths occurred during the trial.

“Obesity medications are a useful adjunct to lifestyle interventions, because many people struggle to lose weight and maintain weight loss with diet and exercise alone,” said Sean Wharton, MD, of the Wharton Weight Management Clinic in Burlington, Ontario, and lead author of the study.

Limitations included the predominance of female patients, which may affect generalizability, and smaller subgroup numbers, which reduced the ability to detect differences across groups. About 20% of patients did not complete the trial, requiring imputation of missing data. The lack of an active comparator, such as a higher oral dose or subcutaneous semaglutide, limited comparisons between formulations.

Researchers concluded that oral semaglutide 25 mg once daily reduced weight more than placebo in patients with overweight or obesity and improved physical function and metabolic measures.

The trial was funded by Novo Nordisk. Researchers reported no deaths and a safety profile consistent with other GLP-1 RAs.

Full disclosures can be found in the published study. 

Source: NEJM