Effect of short-acting exenatide administered three times daily on markers of cardiovascular disease in type 1 diabetes: A randomized double-blind placebo-controlled trial

Diabetes Obes Metab. 2020 Sep;22(9):1639-1647. doi: 10.1111/dom.14078. Epub 2020 Jun 16.

Abstract

Aims: To investigate the effect of adding the short-acting glucagon-like peptide 1 receptor agonist (GLP-1RA) exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes.

Materials and methods: In a randomized, double-blind, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily injection therapy with a body mass index >22.0 kg/m2 and glycated haemoglobin concentration of 59 to 88 mmol/mol (7.5%-10.0%) were randomized (1:1) to preprandial subcutaneous injection of 10 μg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported markers of cardiovascular risk were secondary endpoints and were analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population. The primary results of this study, the MAG1C (Meal-time Administration of exenatide for Glycaemic control in type 1 diabetes Cases) trial, were previously reported.

Results: Exenatide changed total fat mass by -2.6 kg (95% confidence interval [CI] -3.6; -1.6; P < 0.0001) and lean body mass by -1.1 kg (95% CI -1.9; -0.4; P = 0.01) compared with placebo, as assessed by dual-energy X-ray absorptiometry. Fat mass reductions were similar for central and peripheral fat mass. Exenatide did not change levels of interleukin-2 or -6; tumour necrosis factor-α; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (DNA oxidation marker).

Conclusions: Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction, but had no effect on biomarkers of cardiovascular disease risk.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 2*
  • Double-Blind Method
  • Exenatide
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents
  • Venoms

Substances

  • Biomarkers
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Venoms
  • Exenatide