Continued Semaglutide Leads to Further Weight Loss in Patients With Overweight/Obesity

After a 20-week run-in period, adults with overweight or obesity who continued semaglutide for another 48 weeks continued losing weight, while those switched to placebo gained back weight. Researchers published the findings in The Journal of the American Medical Association.

“The benefits of continuing semaglutide treatment for 68 weeks, rather than switching to placebo after 20 weeks, are consistent with findings from other withdrawal trials of antiobesity medications,” researchers wrote. “These results emphasize the chronicity of obesity and the need for treatments that can maintain and maximize weight loss.”

The clinical trial included 803 participants who completed 20 weeks of subcutaneous semaglutide, titrated to 2.4 mg weekly, and achieved an average weight loss of 10.6%. Researchers randomized participants to either continued treatment with subcutaneous semaglutide or placebo, both in addition to lifestyle interventions, for an additional 48 weeks.

According to the study, participants who continued receiving subcutaneous semaglutide had an additional weight loss of 7.9%, on average, over the 48 weeks. Participants who switched to placebo, on the other hand, had average weight gain of 6.9% during the continuation period.

“In those who continued semaglutide after randomization, weight loss achieved during the run-in period not only was sustained but continued, reaching a plateau at week 60 to week 68 and ultimately resulting in an estimated reduction of 17.4% over the entire trial,” researchers reported. “In contrast, participants who switched to placebo at week 20 gradually regained weight.”

Waist circumference, systolic blood pressure, and physical functioning scores also significantly improved with continued semaglutide compared with placebo, the study found. Nearly half of participants on continued semaglutide, compared with 26.1% on placebo, reported gastrointestinal events. However, treatment discontinuation rates due to adverse events were similar between the two groups: 2.4% in the continued semaglutide group and 2.2% in the placebo group.

“These results indicate that most participants tolerated the strict up-titration schedule in the trial, and those who continued treatment at the 2.4-mg/wk dose beyond 20 weeks were unlikely to experience significant tolerability challenges thereafter,” researchers wrote.

Reference:
Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224