Semaglutide produced 18 percent weight loss after bariatric surgery in small trial
A small randomized trial found semaglutide 2.4 mg helped people who had lost little weight after gastric bypass or sleeve gastrectomy, a group with few drug options until now.
A double-blind, placebo-controlled trial found that adults who had lost little weight after bariatric surgery lost an average of 18.0 percent of their body weight after 68 weeks of weekly semaglutide 2.4 mg, compared with a 0.4 percent gain on placebo [1][2]. The trial, called BARI-STEP, was published in Nature Medicine [1][2].
BARI-STEP randomized 70 adults 1:1 to semaglutide 2.4 mg weekly or placebo [1][2]. Participants had a mean age of 47.3 years; 58 of 70, or 82.9 percent, were female, and 12, or 17.1 percent, were male [1][2]. Everyone had undergone Roux-en-Y gastric bypass or sleeve gastrectomy at least one year earlier and was classified as having a suboptimal clinical response, defined as less than 20 percent weight loss from surgery [1][2]. All participants also received a lifestyle intervention with a 500-calorie daily energy deficit [1][2]. The primary outcome was percentage weight loss at week 68, analyzed on an intention-to-treat basis; that analysis included 63 people [1][2].
Weight change from baseline to week 68 averaged −18.0 percent (standard deviation 9.2) with semaglutide (n = 34) versus +0.4 percent (standard deviation 7.0) with placebo (n = 29) [1][2]. The adjusted treatment difference was −19.18 percentage points (95 percent confidence interval −23.4 to −14.8; P < 0.001) [1][2]. The abstract also reports improvement in metabolic parameters and quality of life with semaglutide, but does not give the size of those changes [1][2].
Adverse events were consistent with semaglutide's known safety and tolerability profile, with no new safety concerns for the post-bariatric population, according to the abstract [1][2]. The trial reported eight serious adverse events, one suspected unexpected serious adverse reaction and no treatment-related deaths [1][2]. The abstract does not say how the serious events were divided between the semaglutide and placebo groups [1][2].
Earlier trials tested other GLP-1 drugs in people with a poor response to bariatric surgery. In BARI-OPTIMISE, liraglutide 3.0 mg produced 9.4 percent weight loss at 24 weeks versus 1.1 percent with placebo, a treatment effect of −8.8 percentage points (95 percent CI −11.9 to −5.7) [1]. In the GRAVITAS trial, liraglutide 1.8 mg daily in people with persistent or recurrent type 2 diabetes after surgery produced a mean weight difference of −4.2 kg (95 percent CI −6.8 to −1.4) at 26 weeks [1]. Those studies used different drugs, doses and shorter treatment periods, so their results are not directly comparable to BARI-STEP's [1].
Why it matters for patients
About 20 percent of people who have bariatric surgery have a suboptimal response, and improvement in weight-related conditions such as type 2 diabetes tracks with how much weight is lost, while weight regain can bring those conditions back [1]. Revisional surgery was historically the main option for weight regain, with only modest effects on weight and metabolic health, and drug options for this group have been limited [1].
The dose studied, semaglutide 2.4 mg once weekly, was approved in 2021 for weight management in adults with obesity or overweight plus at least one weight-related condition, alongside a reduced-calorie diet and increased physical activity [1]. The paper does not describe an approval specific to people whose surgery did not work well, and whether insurers or pharmacy benefit managers cover semaglutide for that group has not been reported.
The trial's results reflect the drug plus a structured lifestyle program with a 500-calorie daily deficit, not the drug alone [1]. With 70 people randomized and 63 in the main analysis, and 82.9 percent of participants female, the findings may not represent every post-surgical patient; the standard deviation of 9.2 percentage points means individual results varied widely around the average [1][2].
Whether weight returns after semaglutide is stopped was not measured in this trial, which followed participants through 68 weeks of treatment [1][2].
What happens next
BARI-STEP is registered at ClinicalTrials.gov as NCT05073835 [1][2][3]. No longer-term follow-up, extension study or regulatory filing for this use has been disclosed in the publication [1][2].
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Sources
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