Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials

B. Ahrén*, J.-F. Gautier, R. Berria, W. Stager, R. Aronson, C.J. Bailey

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. Methods: Six randomized, placebo-controlled studies of lixisenatide 20μg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. Results: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9mmol/l, p<0.001) and glucose excursion (LS mean difference vs. placebo: -4.5mmol/l, p<0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0ng/l, p<0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p<0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. Conclusions: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. © 2014 John Wiley and Sons Ltd.

Original languageEnglish
Pages (from-to)861-868
Number of pages8
JournalDiabetes, Obesity and Metabolism
Volume16
Issue number9
Early online date11 Apr 2014
DOIs
Publication statusPublished - 30 Sep 2014

Bibliographical note

Presented at the 73rd Annual Meeting of the American Diabetes Association, 21–25 June 2013, Chicago, IL, USA; 49th Annual Meeting of the European Association for the Study of Diabetes, 23–27 September 2013, Barcelona, Spain.

Keywords

  • diabetes mellitus
  • GLP-1
  • insulin secretion

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