title: Pronounced reduction of postprandial glucagon by lixisenatide: a meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: J-F
authors.initials: JF
authors.lastname: Gautier
authors.forename: R
authors.initials: R
authors.lastname: Berria
authors.forename: W
authors.initials: W
authors.lastname: Stager
authors.forename: R
authors.initials: R
authors.lastname: Aronson
authors.forename: C J
authors.initials: CJ
authors.lastname: Bailey
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D010455:Peptides / Q000627:therapeutic use*; D019518:Postprandial Period; D016032:Randomized Controlled Trials as Topic; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C517652:hemoglobin A1c protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: GLP-1; diabetes mellitus; insulin secretion