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Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk: a meta-analysis of randomized clinical trials




New drugs for type 2 diabetes need to demonstrate their cardiovascular safety, due regulatory requirements from the Food and Drug Administration. For this reason, glucagon-like peptide-1 receptor agonists (GLP-1 RA) are currently undergoing large-scale, long-term randomized trials specifically designed for cardiovascular outcomes. Aim of the present meta-analysis of randomized clinical trials is the assessment of the effects of GLP-1 RA on major cardiovascular events (MACE), mortality and cardiovascular risk factors.


A meta-analysis was performed including all trials with a duration of at least 6 months, comparing a GLP-1 RA with a non-GLP-1 RA agent in type 2 diabetes. MACE and mortality were retrieved and combined to calculate Mantel–Haenzel odds ratio (MH-OR). Furthermore, data on endpoint systolic and diastolic blood pressure, total and high-density lipoprotein (HDL) cholesterol and triglyceride were collected.


Of 37 selected trials, 33 reported information on MACE, and 25 reported at least one event. The difference in the incidence of MACE between GLP-1 RA and comparators did not reach statistical significance [MH-OR 0.78 (0.54–1.13), p = 0.18]. GLP-1 RA were associated with a significant reduction in the incidence of MACE in comparisons with placebo and pioglitazone, with a non-significant trend towards reduction in DPP4i-controlled studies. No significant effect of GLP-1 RA was observed on mortality, although a non-significant favourable trend was observed in comparisons with placebo.


The present meta-analysis confirms the cardiovascular safety of GLP-1 RA, at least in the short term and in low-risk individuals. GLP-1 RA could have a beneficial effect on the incidence of MACE, at least in comparison with placebo.