Cardiovascular safety of GLP-1 receptor agonists for diabetes patients with high cardiovascular risk: A meta-analysis of cardiovascular outcomes trials

Aim: To show long-term cardiovascular safety of the GLP-1 receptor agonists for diabetes patients with cardiovascular risk.

Methods: For cardiovascular outcomes, the association between treatment and outcomes was estimated using the odds ratio and 95% confidence interval. I² test was adopted to assess the magnitude of heterogeneity between studies, with values more than 25%, 50%, and 75% defined as low, moderate, or high heterogeneity.

Results: We combined data from four cardiovascular outcomes trials and prospectively blinded endpoint adjudication. 4105 cardiovascular events including cardiovascular death, acute MI or stroke experienced during the trials. And the odds ratios of the cardiovascular outcomes were 0.90 (95% CI 0.81, 1.00) for the cardiovascular outcome, 0.93 (95% CI 0.85, 1.02) for nonfatal myocardial infarction, 0.88 (95% CI 0.76, 1.03) for nonfatal stroke, 0.94 (95% CI 0.84, 1.05) for heart failure hospitalization, 0.89 (95% CI 0.63, 1.27) for pancreatitis, 0.98 (95% CI 0.92, 1.05) for any hypoglycemic events, 0.92 (95% CI 0.83, 1.01) for the severe hypoglycemic events, 0.96 (95% CI 0.83, 1.01) for serious adverse events. Significant differences showed in mortality parameters: 0.88 (95% CI 0.81, 0.95) for all-cause mortality, 0.87 (95% CI 0.79, 0.97) for cardiovascular mortality. CV benefits were obtained in the male, black, Asian patients and patients with BMI ≥ 30 kg/m².

Conclusion: Additional GLP-1 receptor agonists treatment did not increase cardiovascular outcomes in diabetes patients with high cardiovascular risk or established cardiovascular disease.