Cardiovascular effectiveness of human-based vs. exendin-based glucagon like peptide-1 receptor agonists: a retrospective study in patients with type 2 diabetes

AIMS: Glucagon like peptide-1 (GLP-1) receptor agonists (GLP-1RA) are effective to control type 2 diabetes (T2Ds) and can protect from adverse cardiovascular outcomes. GLP-1RA are based on the human GLP-1 or the exendin-4 sequence. We compared cardiovascular outcomes of patients with T2D who received human-based or exendin-based GLP-1RA in routine clinical practice. METHODS AND RESULTS: We performed a retrospective study on the administrative database of T2D patients from the Veneto Region (North-East Italy). We identified patients who initiated a human-based or exendin-based GLP-1RA from 2011 to 2018. The primary outcome was occurrence of major adverse cardiovascular events (MACE). Secondary outcomes were individual MACE components, revascularization, hospitalization for heart failure, or for cardiovascular causes. From 330 193 patients with diabetes, 6620 were new users of GLP-1RA. After propensity score matching, we analysed 1098 patients in each group, who were on average 61 years old, 59.5% males, 13% with established cardiovascular disease, had an estimated diabetes duration of 8.4 years, and a baseline HbA1c of 7.9%. During a median follow-up of 18 months, patients treated with human-based GLP-1RA as compared to those treated with exendin-based GLP-1RA, showed lower rates of MACE [hazard ratio 0.61; 95% confidence interval (CI) 0.39-0.95], myocardial infarction (0.51; 95% CI 0.28-0.94), and hospitalization for cardiovascular causes (0.66; 95% CI 0.47-0.92). CONCLUSION: We observed better cardiovascular outcomes among patients treated with human-based vs. exendin-based GLP-1RA under routine care. In the absence of comparative trials and in view of the limitations of retrospective studies, this finding provides a moderate level of evidence to guide clinical decision.