Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Diabetes Obes Metab. 2015 Nov;17(11):1065-74. doi: 10.1111/dom.12541. Epub 2015 Sep 23.

Abstract

Aim: To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.

Results: In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was -0.66% [six studies; 95% confidence interval (CI) -1.14 to -0.19; I(2) = 88%] with albiglutide, and -1.18% (seven studies; 95% CI -1.34 to -1.02; I(2) = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences -0.40%; 95% CI -0.66 to -0.14; I(2) = 85%, -0.44%; 95% CI -0.58 to -0.29; I(2) = 40% and -0.28; 95% CI -0.45 to -0.10; I(2) = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.

Conclusions: Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.

Keywords: GLP-1; GLP-1 analogue; incretin therapy; meta-analysis; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / analogs & derivatives
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Immunoglobulin Fc Fragments / administration & dosage
  • Incretins / administration & dosage*
  • Male
  • Metformin / administration & dosage
  • Peptides / administration & dosage
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins / administration & dosage
  • Venoms / administration & dosage

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Incretins
  • Peptides
  • Recombinant Fusion Proteins
  • Venoms
  • hemoglobin A1c protein, human
  • rGLP-1 protein
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Metformin
  • Exenatide
  • dulaglutide