Semaglutide, a once-weekly glucagon-like peptide-1 analog for type 2 diabetes, showed significant, clinically meaningful reductions in HbA1c and body weight in the SUSTAIN clinical trial program. Higher body mass index (BMI) at baseline (BL) was associated with greater weight loss during semaglutide therapy. This post hoc analysis evaluated change in HbA1c by BL BMI (<25, 25-<30, 30-<35 and ≥35 kg/m2) for semaglutide vs. comparators by trial for SUSTAIN 1-5 and 7. Safety data were pooled and analyzed stratified by trial. Reductions in mean HbA1c (%) from BL were greater in all BMI subgroups with semaglutide vs. comparators (Figure). There were no significant interactions between treatment and BMI, indicating a consistent effect of semaglutide vs. comparator on change in HbA1c across BMI subgroups. In all treatment arms, adverse events (AEs) occurred in a similar proportion of subjects across BMI subgroups. Gastrointestinal AEs were higher with semaglutide, but decreased with increasing BL BMI, vs. comparators (semaglutide: <25 kg/m2=48.8%, 25-<30 kg/m2=43.0%, 30-<35 kg/m2=39.4% and ≥35 kg/m2 =39.3% vs. comparators range: 21.2-28.9%). Premature treatment discontinuation due to AEs was higher in all BMI subgroups with semaglutide vs. comparators (5.6-15.3% vs. 2.3-8.3%).

In conclusion, the efficacy of semaglutide in lowering HbA1c does not appear to be influenced by BL BMI. Semaglutide had an acceptable safety profile in all BMI subgroups.


A. Viljoen: Advisory Panel; Self; NAPP Pharmaceuticals Limited. Research Support; Self; Eli Lilly and Company, Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck & Co., Inc., Sanofi. T. Gondolf: Employee; Spouse/Partner; Chr. Hansen Holding A/S. Employee; Self; Novo Nordisk A/S. O. Hansen: Employee; Self; Novo Nordisk A/S. N. Wijayasinghe: None. J. Unger: Advisory Panel; Self; Abbott Laboratories, Novo Nordisk Inc. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.


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