Cardiovascular events associated with second-line anti-diabetes treatments: analysis of real-world Korean data

Abstract

AIM: To compare the risks of cardiovascular disease (CVD) and all-cause mortality associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP4i) and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy in people with Type 2 diabetes. METHODS: We identified 40 263 individuals who used SU (n = 11 582), DPP4i (n = 26 623) or TZD (n = 2058) in addition to MET between January 2013 and June 2015 from the database of the Korean National Health Insurance, the single-payer healthcare system in South Korea. Cox proportional hazard models were used to estimate hazard ratios for major CVD event (coronary artery disease, heart failure, stroke or transient ischaemic attack) development and all-cause mortality by second-line anti-diabetes medication type. Age, sex, duration of MET monotherapy, calendar year and comorbid conditions were adjusted as potential confounders. RESULTS: The observed numbers of CVD events (total observed person-time) were 485 (18 778 person-years) for MET + SU, 744 (40 374 person-years) for MET + DPP4i and 60 (3014 person-years) for MET + TZD users. Compared with MET + SU users, the fully adjusted hazard ratios for CVD events were 0.79 [95% confidence interval (CI): 0.71-0.89] for MET + DPP4i users and 0.85 (95% CI: 0.65-1.11) for MET + TZD users. The corresponding hazard ratios for all-cause mortality were 0.84 (95% CI: 0.66-1.07) for MET + DPP4i users and 0.67 (95% CI: 0.35-1.28) for MET + TZD users. CONCLUSION: Analysis of Korea National Health Insurance database showed that MET + DPP4i treatment for diabetes had a lower CVD risk than MET + SU treatment.