Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study

Abstract

BACKGROUND: The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015. Incident users of sulfonylurea and DPP-4i who were not prescribed the comparator drug in the year before treatment initiation were included. DPP-4i-treated and sulfonylurea-treated patients were matched on propensity score, calculated with >40 variables. The risk of hospitalization for HF was evaluated with a Cox proportional hazards model in 255 691 matched pairs. Analyses were conducted in the total patient population and in both strata divided by the presence of cardiovascular disease during the baseline period. The hazard ratios (HRs) of hospitalization for HF for DPP-4i-treated patients were 0.78 (95% confidence interval [CI], 0.67-0.86) in all of the patients, 0.77 (95% CI, 0.68-0.79) in patients with baseline cardiovascular disease, and 0.71 (95% CI, 0.56-0.90) in patients without baseline cardiovascular disease compared with HRs for sulfonylurea-treated patients. Sitagliptin and linagliptin showed statistically lower risk for hospitalization for HF (HR, 0.76: 95% CI, 0.67-0.86 for sitagliptin-prescribed patients: HR, 0.74: 95% CI, 0.59-0.92 for linagliptin-prescribed patients) than for sulfonylurea. The HRs for hospitalization for myocardial infarction and stroke with the use of a DPP-4i versus sulfonylurea were HR, 0.76 (95% CI, 0.67-0.87) and HR, 0.63 (95% CI, 0.60-0.67), respectively. CONCLUSIONS: Our findings suggest that DPP-4i use did not increase the risk of HF compared with sulfonylurea. In addition, the risks for cardiovascular outcomes were not elevated in DPP-4i-treated patients compared with sulfonylurea-treated patients.