Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme

Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.

Abstract

Aim: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects.

Materials and methods: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol-specified composite endpoint was the proportion of participants achieving HbA1c <53 mmol/mol (7.0%) at end of treatment (30 or 56 weeks) without weight gain and with no severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia. A post hoc composite endpoint was the proportion of participants achieving the primary composite endpoint without moderate or severe GI adverse events (AEs).

Results: Across the SUSTAIN trials 1 to 5, 3918 participants with T2D were randomized to once-weekly subcutaneous semaglutide 0.5 mg, 1.0 mg, or comparators (placebo, sitagliptin 100 mg, exenatide extended release 2.0 mg or insulin glargine). The proportion of participants achieving HbA1c <53 mmol/mol (7.0%) with no weight gain and no severe/BG-confirmed symptomatic hypoglycaemia was 47% to 66% (semaglutide 0.5 mg) and 57% to 74% (semaglutide 1.0 mg) vs 7% to 19% (placebo) and 16% to 29% (active comparators; all P < .0001). More participants achieved the primary composite endpoint with no moderate or severe GI AEs with semaglutide vs comparators (all P < .0001).

Conclusion: Semaglutide helped more people with T2D achieve HbA1c targets than did comparators in the SUSTAIN 1 to 5 trials, while avoiding unwanted outcomes such as weight gain, hypoglycaemia and GI side effects.

Keywords: GLP-1; glycaemic control; hypoglycaemia; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / epidemiology
  • Glucagon-Like Peptides / therapeutic use*
  • Glycated Hemoglobin A / drug effects*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Male
  • Middle Aged
  • Multicenter Studies as Topic / statistics & numerical data
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Retrospective Studies
  • Weight Gain / drug effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • semaglutide
  • Glucagon-Like Peptides