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

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.