Dipeptidyl Peptidase-4 Inhibitors and Heart Failure: Friends or Foes?

Heart failure (HF) is one of the leading causes of morbidity and mortality. Several risk factors have been identified that have been consistently associated with the development of HF, including type 2 diabetes and glucose-lowering agents. However, different drugs for type 2 diabetes may have diverse, and even divergent, effects on heart failure. The insulin-sensitizing thiazolidinediones have been associated with increased rates of HF in randomized controlled trials, whereas for other drugs, this relationship is less clear. Before the publication of the SAVOR-TIMI53 trial, available data suggested that DPP4 inhibitors could have a protective effect with respect to incident HF. The possibility of a causal finding cannot be ruled out, but it appears rather unlikely, considering that another cardiovascular outcome study showed a trend toward an increased risk with a different molecule of the same class, and that some epidemiological studies associated sitagliptin to an increased risk of HF. This review explores the possible mechanisms underlying the association of DPP4 inhibitor use with an increased risk for incident HF.