Dipeptidyl Peptidase‐4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus and End‐Stage Renal Disease Requiring Dialysis

INTRODUCTION: Evidence on the safety of antidiabetic agents in end-stage renal disease (ESRD) patients requiring dialysis, a group often excluded from randomized controlled trials, is scant. Dipeptidyl peptidase-4 inhibitors (DPP-4i), widely used for type 2 diabetes mellitus (T2DM) management in this group, have raised concerns regarding the risk of heart failure (HF). However, real-world evidence on HF risk with DPP-4i in dialysis-dependent diabetic patients is limited. We aimed to assess HF safety of DPP-4i compared with sulfonylureas (SU)/meglitinides in a nationwide T2DM population with ESRD requiring dialysis. METHODS: A new user, active comparator cohort study employing propensity score-inverse probability of treatment weighting was conducted utilizing Taiwan's nationwide healthcare claims database (2012-2020). Evaluated outcomes included hospitalizations for HF or cardiovascular death as the primary outcome, with major adverse cardiovascular events (MACEs), all-cause mortality, and severe hypoglycemia as secondary outcomes, using weighted Cox proportional hazards models. RESULTS: The study included 6882 patients initiating DPP-4i and 6174 starting SU/meglitinides, with a mean age of 66.4 years and 53.1% male. Initiation of DPP-4i versus SU/meglitinide was not associated with increased risks of HF hospitalizations, cardiovascular death, MACEs, or all-cause mortality, but was significantly tied to a 44% reduced risk of severe hypoglycemia. CONCLUSIONS: This study's findings indicate that in T2DM patients with ESRD requiring dialysis, DPP-4i do not elevate the risk of hospitalizations for HF, cardiovascular death, or all-cause mortality, but significantly lower the risk of severe hypoglycemia compared with SUs/meglitinides. This supports the preference for DPP-4i over SUs or meglitinides for managing T2DM in dialysis patients.