Dipeptidyl Peptidase‐4 Inhibitors Associated Heart Failure Events in Adult Patients With Type‐2 Diabetes Mellitus Treated With Dipeptidyl Peptidase‐4 Inhibitors: A Systematic Review and Meta‐Analysis

INTRODUCTION: DPP-4 inhibitors use has been reported to cause heart failure events in patients with type-2 diabetes. The FDA had also issued warnings concerning increased risk of heart failure events for alogliptin, saxagliptin and their combination with metformin. METHODS: Randomized controlled trials (RCTs) involving adult patients with type-2 diabetes patients with or without history of cardio-vascular disorders were included in the review. Cohort studies, case-control studies and other non-RCTs, and studies involving paediatric patients were excluded. Data bases searched were PubMed/Medline, DOAJ, MDPI, Google Scholar and clinicaltrails.gov. The search was conducted in late January of 2026. Risk of bias was assessed using RoB-2 tool for RCTs. Individual study outcomes were tabulated and summary measure was synthesized by meta-analysis under random effect model; GRADE certainty of evidence was used; sub-group analysis based on individual DPP-4 inhibitors, follow-up duration and placebo or other controls was done; systematic review was done under PRISMA 2020 Guidelines. RESULTS: The meta-analysis was done under random effect computation model for all 29 included studies. The analysis for total of pooled 67,873 patients showed statistically insignificant association between the use of DPP-4 inhibitors and heart failure with Risk Ratio (RR) = 1.06, 95% Confidence Interval (CI) 0.94-1.12. Sub-group analysis found significant association of saxagliptin use with increased heart failure risk. CONCLUSION: Results should be interpreted with caution because of several limitations of the study. TRIAL REGISTRATION: PROSPERO, CRD420261288081.