Effect of Glucagon-like Peptide-1 Receptor Agonists on All-cause Mortality and Cardiovascular Outcomes: A Meta-analysis

Curr Diabetes Rev. 2018;14(3):273-279. doi: 10.2174/1573399813666170414101450.

Abstract

Background: Cardiovascular disease is the leading cause of death in patients with type 2 diabetes.

Objective: To assess the impact of glucagon-like peptide-1 receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant outcomes including all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart failure, in patients with type 2 diabetes.

Methods: EMBASE, MEDLINE, and CENTRAL were searched (inception to September 2016) for randomized, double-blind, placebo-controlled trials of at least one year in duration that compared any GLP1RA to placebo in patients with type 2 diabetes. Both authors independently completed the literature search, data extraction, and risk of bias assessment. For each outcome, a Risk Ratio (RR) and 95% Confidence Interval (CI) were calculated using a Mantel-Haenszel random effects model.

Results: Eight trials (three albiglutide, two lixisenatide, two liraglutide, one semaglutide) consisting of 21,135 patients were included. Most patients had, or were at high risk for, cardiovascular disease. Follow- up ranged from 1-3.8 years. Trials contributing the majority of data were deemed to have a low risk of bias. The risk of all-cause mortality was lowered by 11% in patients receiving a GLP1RA (RR 0.89, 95% CI 0.81-0.99). There was no statistically significant difference between groups with respect to cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalizations for heart failure.

Conclusion: GLP1RA therapy when compared to placebo reduced all-cause mortality in high cardiovascular risk patients with type 2 diabetes. They did not impact cardiovascular mortality, nonfatal MI, nonfatal stroke, or heart failure hospitalizations.

Keywords: Glucagon-like peptide-1 receptor agonists; cardiovascular diseases; hypoglycemic agents; incretins; liraglutide; type 2 diabetes mellitus..

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetic Angiopathies / mortality
  • Diabetic Angiopathies / prevention & control
  • Double-Blind Method
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptides / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide / therapeutic use
  • Peptides / therapeutic use
  • Randomized Controlled Trials as Topic / statistics & numerical data

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptides
  • semaglutide
  • Glucagon-Like Peptides
  • lixisenatide
  • Liraglutide