Update in Cardiovascular Safety of Glucagon Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes. A Mixed Treatment Comparison Meta-Analysis of Randomised Controlled Trials

Heart Lung Circ. 2018 Nov;27(11):1301-1309. doi: 10.1016/j.hlc.2018.03.018. Epub 2018 Mar 29.


Background: The aim of this mixed treatment comparison (MTC) meta-analysis was to determine glucagon like peptide-1 (GLP-1) receptor agonists' effects on cardiovascular (CV) outcomes in patients with type 2 diabetes (T2DM).

Methods: A comprehensive, systematic review was conducted using EMBASE and Medline databases. All included trials were large CV outcome trials of GLP-1 agonists versus placebo in T2DM. The primary outcomes of this MTC meta-analysis were death from CV causes, non-fatal MI, and non-fatal stroke. Hospitalisation for heart failure (HF) was evaluated as a secondary endpoint.

Results: A total of four trials, including 33,457 patients, met eligibility criteria and were retained for the meta-analysis. Our pairwise meta-analysis results showed a 13% reduction in death from cardiovascular causes in patients who received GLP-1 agonists versus placebo (RR 0.87, 95% CI: 0.78-0.96). However, no statistically significant reduction was observed with GLP-1 agonists in terms of reducing non-fatal MI (RR 0.95, 95% CI: 0.86-1.04), non-fatal stroke events (RR 0.89, 95% CI: 0.76-1.03), and rates of HF hospitalisation (RR 0.94, 95% CI: 0.84-1.04). The network meta-analysis (NMA) showed no significant differences among all the interventions.

Conclusion: Glucagon like peptide-1 therapy was associated with a significant reduction in cardiovascular (CV) death. However, GLP-1 agonists seem to have a safety profile comparable to placebo in terms of reducing non-fatal myocardial infarction (MI), non-fatal stroke events, and rates of HF hospitalisation.

Keywords: Cardiovascular disease; Glucagon like peptide-1 receptor; Meta-analysis; Network meta-analysis; Type 2 diabetes mellitus.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Global Health
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Liraglutide / therapeutic use*
  • Morbidity / trends
  • Network Meta-Analysis*
  • Randomized Controlled Trials as Topic
  • Survival Rate / trends


  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Liraglutide