Cardiovascular safety of evogliptin in patients with type 2 diabetes mellitus: a nationwide cohort study.

Background Cardiovascular safety of evogliptin, a novel dipeptidyl peptidase-4 inhibitor (DPP-4i), remains unclear with limited real-world evidence available on its use. We aimed to assess whether the use of evogliptin was associated with an increased risk of cardiovascular events when compared to glimepiride in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a population-based cohort study using South Korea's nationwide healthcare database from 1 January 2014 to 31 December 2018. We identified a base cohort of patients with T2DM who newly initiated metformin monotherapy and from this cohort, identified a study cohort of patients who either added or switched to glimepiride or DPP-4is (including evogliptin). Patients were followed-up from initiation of DPP-4is or glimepiride until the earliest of outcome occurrence or 31 December 2018. Our primary outcome was hospitalization or emergency visit for cardiovascular events, a composite endpoint comprised of cerebrovascular events, heart failure, myocardial infarction, transient ischaemic attack, angina pectoris, and revascularization procedures; secondary outcomes were the individual components of the primary outcome. A multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of study outcomes associated with evogliptin when compared to glimepiride. Results Our base and study cohorts had 317,307 and 128,788 patients, respectively, of which 100,038 were DPP-4i users (2,946 were evogliptin users) and 28,750 were glimepiride users within the study cohort. The median follow-up was 195 days for evogliptin and 113 days for glimepiride users. Compared with glimepiride, evogliptin was associated with a reduced risk of the primary outcome (aHR 0.67, 95% CI 0.48-0.95) and cerebrovascular events (aHR 0.41, 95% CI 0.22-0.78) but showed non-significant associations for myocardial infarction (aHR 0.63, 95% CI 0.27-1.46), heart failure (aHR 0.35, 95% CI 0.09-1.47), transient ischaemic attack (aHR 0.23, 95% CI 0.03-1.72), and angina pectoris (aHR 1.35, 95% CI 0.82-2.21). Conclusions Findings from this population-based cohort study provide novel real-world evidence in that use of evogliptin, as compared with glimepiride, did not increase the risk of cardiovascular events, including cerebrovascular events, myocardial infarction, heart failure, transient ischemic attack, and angina pectoris. This article is protected by copyright. All rights reserved.