Semaglutide versus placebo in individuals with poor weight loss after bariatric surgery: a double-blinded, randomized, placebo-controlled trial

A suboptimal clinical response after metabolic and bariatric surgery (MBS) is common and carries considerable health concerns. Here a double-blinded, randomized (1:1), placebo-controlled trial using semaglutide 2.4 mg weekly (BARI-STEP) recruited adult participants at least 1 year after gastric bypass or sleeve gastrectomy with a suboptimal clinical response, defined as less than 20% weight loss from surgery. This was an adjunct to lifestyle intervention with a 500-kcal daily energy deficit. The primary outcome was percentage weight loss after 68-week treatment on an intention-to-treat analysis. Seventy participants (mean (s.d.) age = 47.3 (10.3) years, 58 (82.9%) female and 12 (17.1%) male) were randomized to receive 2.4 mg semaglutide (n = 35) or placebo (n = 35). The intention-to-treat sample included 63 participants. Estimated change in mean (s.d.) percentage weight loss from baseline to week 68 was -18.0 (9.2) with semaglutide 2.4 mg (n = 34) versus +0.4 (7.0) with placebo (n = 29). The mean adjusted treatment difference in percentage body weight change for semaglutide 2.4 mg versus placebo was -19.18 (95% confidence interval -23.4 to -14.8; P < 0.001). Adverse events (AEs) were consistent with the known safety and tolerability profile of semaglutide, with no new safety concerns for the post-bariatric population. There were eight serious AEs, one suspected unexpected serious adverse reaction and no treatment-related deaths. BARI-STEP demonstrates that in people with a suboptimal clinical response after MBS, semaglutide results in substantial and clinically significant body weight reduction along with improvement in metabolic parameters and quality of life, compared to placebo. These findings suggest that semaglutide 2.4 mg is a safe and effective treatment option for this patient population. ClinicalTrials.gov: NCT05073835 .