Source: Yu, et al. Diabetes Care 2015;38:

The class of medications used to treat diabetes (and obesity) known as “the incretins” includes several DPP4 inhibitors and GLP1 agonists. These agents have achieved a favorable status in prescribing algorithms because of the combination of their low risk of hypoglycemia, impact upon weight (neutral for DPP4, weight loss for GLP1), and effects on postprandial glucose attributed to glucagon blunting.

Nonetheless, analysis of the SAVOR-TIMI trial, in which a 27% increased risk of congestive heart failure (CHF) was found in persons taking saxagliptin compared to placebo spurred concerns that incretins might worsen risk for CHF. Other trials with other DPP4 inhibitors did not find a statistically significant increased CHF risk (e.g., the EXAMINE trial with alogliptin).

Yu et al performed a nested case-control analysis of diabetic patients who received new prescriptions for antidiabetic drugs and were free of CHF at that time. They compared incidence of CHF in patients who had been prescribed incretins vs two or more other oral agents for their diabetes.

Among a population of 57,737 diabetics, 1118 incident cases of CHF were identified. Incident CHF was not more common in persons prescribed incretins; to the contrary, there was a trend toward less CHF in incretin-treated patients (odds ratio = 0.85, confidence interval, 0.62-1.16). These data are reassuring about the safety profile of incretins in regards to CHF.