Semaglutide versus placebo in individuals with poor weight loss after bariatric surgery: a double-blinded, randomized, placebo-controlled trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: 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 .
Source: Nature Medicine
Authors: Chloe Stanley, Ritwika Mallik, Nausheen Hamid, Friedrich C. Jassil, Victoria Reuven, Tapiwa Ruwona, Samuel J. Dicken, Sulmaaz Qamar, Benjamin Norton, Helen Kingett, Andrea Pucci, Cormac Magee, David Boniface, Rachel L. Batterham, Kalpana Devalia, Jessica Mok, Mohamed Elkalaawy, John Loy, Andrew Jenkinson, Haris Markakis, Marco Adamo, Alanna Brown, Janine Makaronidis
Institutions: National Institute for Health and Care Research, UCL Biomedical Research Centre, University College London, Queen Mary University of London, Barts Health NHS Trust, Blizard Institute, University College Hospital, University College London Hospitals NHS Foundation Trust, University Hospital of Geneva, Deutsches Diabetes-Zentrum e.V., Heinrich Heine University Düsseldorf, Cleveland Clinic London, Ashford and St Peter's Hospitals NHS Foundation Trust, Homerton University Hospital
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Agriculture, Eli Lilly and Company, Pfizer, ViiV Healthcare, National Institute for Health and Care Research, Sir Jules Thorn Charitable Trust, Society for Endocrinology, Novo Nordisk, University College London Hospitals NHS Foundation Trust, National Institute of Food and Agriculture, UCLH Biomedical Research Centre
Award: G7339021037
OpenAlex ID: W7162104885