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

Diabetes Obes Metab. 2014 Sep;16(9):861-8. doi: 10.1111/dom.12290. Epub 2014 Apr 11.


Aim: 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 20 µg 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: -4.9 mmol/l, p < 0.001) and glucose excursion (LS mean difference vs. placebo: -4.5 mmol/l, p < 0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0 ng/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.

Keywords: GLP-1; diabetes mellitus; insulin secretion.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Gastric Emptying / drug effects
  • Glucagon / blood*
  • Glucagon / drug effects
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / agonists*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Peptides / therapeutic use*
  • Postprandial Period
  • Randomized Controlled Trials as Topic


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Peptides
  • hemoglobin A1c protein, human
  • lixisenatide
  • Glucagon-Like Peptide 1
  • Glucagon