GLP-1 Receptor Agonists and Cardiovascular Disease: a Meta-Analysis of Recent Cardiac Outcome Trials

Cardiovasc Drugs Ther. 2018 Feb;32(1):65-72. doi: 10.1007/s10557-018-6773-2.

Abstract

Purpose: The aim of this study is to examine the cardioprotective properties of Glucagon-like peptide-1 receptor agonist, a class of antihyperglycemic therapy, via meta-analysis of four recently published cardiovascular outcomes trials.

Methods: Meta-analysis was performed pooling data from the ELIXA, LEADER, SUSTAIN-6 and EXSCEL trials. A random effects model was used to generate risk ratio with 95% confidence interval for cardiovascular and safety outcomes.

Results: A total of 33,457 patients were included in the meta-analysis. Based on the study, GLP-1R agonists significantly reduced all-cause mortality (RR 0.89; 95% CI 0.82 to 0.96) and cardiovascular mortality (RR 0.88; 95% CI 0.80 to 0.97) when compared to placebo. When long-acting agents were analyzed alone, reduction in major adverse cardiac events (RR 0.88; 95% CI 0.81 to 0.97) and non-fatal strokes (RR 0.87; 95% CI 0.76 to 0.99) also showed significance.

Conclusion: Overall, GLP-1R agonists appear to have cardioprotective properties likely via modification of metabolic parameters such as glycemic control, weight loss, and improvement in blood pressure. Additional studies are warranted to compare cardiovascular outcomes among the different agents.

Keywords: Cardiovascular outcomes; GLP-1 receptor agonist; Type 2 diabetes mellitus.

Publication types

  • Meta-Analysis

MeSH terms

  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / physiopathology
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Cardiovascular Agents
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins