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

Bo Ahrén, Stephen Atkin, Guillaume Charpentier, Mark L. Warren, John P.H. Wilding, Sune Birch, Anders Gaarsdal Holst, Lawrence A. Leiter

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2210-2219
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

Fingerprint

Type 2 Diabetes Mellitus
Weight Loss
Body Mass Index
Nausea
Vomiting
Glucagon-Like Peptide 1
semaglutide
Therapeutics
Placebos
Body Weight
Pharmaceutical Preparations

Keywords

  • BMI
  • gastrointestinal adverse events
  • GLP-1 analogue
  • GLP-1 based therapy
  • nausea
  • type 2
  • vomiting
  • weight control
  • weight loss

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

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. / Ahrén, Bo; Atkin, Stephen; Charpentier, Guillaume; Warren, Mark L.; Wilding, John P.H.; Birch, Sune; Holst, Anders Gaarsdal; Leiter, Lawrence A.

In: Diabetes, Obesity and Metabolism, Vol. 20, No. 9, 01.09.2018, p. 2210-2219.

Research output: Contribution to journalArticle

Ahrén, Bo ; Atkin, Stephen ; Charpentier, Guillaume ; Warren, Mark L. ; Wilding, John P.H. ; Birch, Sune ; Holst, Anders Gaarsdal ; Leiter, Lawrence A. / 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. In: Diabetes, Obesity and Metabolism. 2018 ; Vol. 20, No. 9. pp. 2210-2219.
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AU - Warren, Mark L.

AU - Wilding, John P.H.

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AU - Holst, Anders Gaarsdal

AU - Leiter, Lawrence A.

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