Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials

Research output: Contribution to journalArticle

Abstract

Aims: To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once-weekly glucagon-like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3-6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contributing factors to weight loss are not established. Materials and Methods: Subjects with inadequately controlled type 2 diabetes (drug-naïve or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. Change from baseline in body weight was assessed within each trial and subgroup. A mediation analysis separated weight loss into direct or indirect (mediated by nausea or vomiting) effects. Results: Clinically relevant weight-loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects). Conclusions: In SUSTAIN 1 to 5, semaglutide-induced weight loss was consistently greater versus comparators, regardless of baseline BMI. The contribution of nausea or vomiting to this weight loss was minor.

Details

Authors
  • Bo Ahrén
  • Stephen L. Atkin
  • Guillaume Charpentier
  • Mark L. Warren
  • John P.H. Wilding
  • Sune Birch
  • Anders Gaarsdal Holst
  • Lawrence A. Leiter
Organisations
External organisations
  • Weill Cornell Medical College Qatar
  • Centre Hospitalier Gilles de Corbeil
  • University of Liverpool
  • Novo Nordisk A/S
  • St. Michael's Hospital
  • Physicians East
  • University of Toronto
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • BMI, gastrointestinal adverse events, GLP-1 analogue, GLP-1 based therapy, nausea, type 2, vomiting, weight control, weight loss
Original languageEnglish
Pages (from-to)2210-2219
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number9
Publication statusPublished - 2018 Sep 1
Publication categoryResearch
Peer-reviewedYes