Cardiovascular Safety of Dipeptidyl-Peptidase IV Inhibitors: A Meta-Analysis of Placebo-Controlled Randomized Trials

• Published in: American journal of cardiovascular drugs : drugs, devices, and other interventions Vol. 17; no. 2; pp. 143 - 155
• Main Authors: Elgendy, Islam Y., Mahmoud, Ahmed N., Barakat, Amr F., Elgendy, Akram Y., Saad, Marwan, Abuzaid, Ahmed, Wayangankar, Siddarth A., Bavry, Anthony A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2017; Springer Nature B.V
• Subjects: Cardiology; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - epidemiology; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Health risk assessment; Heart attacks; Heart failure; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Medicine; Medicine & Public Health; Meta-analysis; Mortality; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Randomized Controlled Trials as Topic; Stroke; Studies; Heart Failure; Sitagliptin; Cardiovascular Outcome; Vildagliptin; Ischemic Stroke
• ISSN: 1175-3277; 1179-187X
• DOI: 10.1007/s40256-016-0208-x

Background Large randomized trials have shown conflicting evidence regarding the cardiovascular safety of dipeptidyl-peptidase 4 (DPP-4) inhibitors. Systematic reviews have been limited by incomplete data and inclusion of observational studies. This study aimed to systematically evaluate the cardiovascular safety of DPP-4 inhibitors in patients with type 2 diabetes. Methods Electronic databases were searched for randomized trials that compared DPP-4 inhibitors versus placebo and reported cardiovascular outcomes. The main outcome assessed in this analysis was heart failure. Other outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, and ischemic stroke. Summary odds ratios (ORs) were primarily constructed using Peto’s model. Results A total of 90 trials with 66,730 patients were included. Compared with placebo, DPP-4 inhibitors were associated with a non-significant increased risk of heart failure [OR 1.11, 95% confidence interval (CI) 0.99–1.25, P  = 0.07] at a mean of 108 weeks. The risk of all-cause mortality (OR 1.03, 95% CI 0.94–1.12, P  = 0.53), cardiovascular mortality (OR 1.02, 95% CI 0.92–1.14, P  = 0.72), myocardial infarction (OR 0.98, 95% CI 0.88–1.09, P  = 0.69), and ischemic stroke (OR 0.99, 95% CI 0.85–1.15, P  = 0.92) was similar between both groups. Conclusion In patients with type 2 diabetes, the safety profile of DPP-4 inhibitors is similar to placebo. As a class, there is only weak evidence for an increased risk of heart failure.