Increased Risk Of Hospitalization For Heart Failure With Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors And Pioglitazone Using The Korean Health Insurance Claims Database (Diabetes Metab J 2015; 39:247-52)

Dipeptidyl peptidase-4 (DPP-4) inhibitors are now being widely used for the treatment of type 2 diabetes, and preclinical studies and short-term clinical studies suggested that DPP-4 inhibitors as well as GLP-1 receptor agonists have cardiovascular (CV) benefits beyond the glycemic effects [1]. However, two randomised clinical trials (RCTs) with saxagliptin [2] and alogliptin [3], separately, in patients with type 2 diabetes at high CV risk showed a rather disappointing neutral CV effect. In the saxagliptin RCT (saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction [SAVOR-TIMI]), more patients in the saxagliptin than in the placebo group were hospitalized for heart failure (HF), whereas in the Examination of Cardiovascular Outcomes with Alogliptin vs. Standard of Care (EXAMINE) trial, alogliptin did not increase the risk of HF outcomes in patients with type 2 diabetes and recent acute coronary syndromes [4]. Then, concerns about HF associated with the use of DPP-4 inhibitors led to many systematic reviews and meta-analyses. In addition to many previous studies, the largest meta-analysis study of recent years showed that a long-term treatment with DPP-4 inhibitors significantly increased the risk of HF [5].