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.

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.

• Authors: Nicklas J Johansen, Thomas F Dejgaard, Asger Lund, Camilla Schlüntz, Emil L Larsen, Henrik E Poulsen, Jens P Goetze, Holger J Møller, Tina Vilsbøll, Henrik U Andersen, Filip K Knop
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 22 Issue 9 Pg. 1639-1647 (09 2020) ISSN: 1463-1326 [Electronic] England
• PMID: 32543021 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

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

Topics

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