Almost 50% of patients with type 2 diabetes will develop heart failure. Data on the effects of glucose-lowering agents on heart failure outcomes have demonstrated that thiazolidinedione’s have a strong and consistent relationship with heart failure. Therefore, Thiazolidinedione use should be avoided in patients with symptomatic heart failure. Recent studies have now examined the relationship between dipeptidyl peptidase 4 (DPP-4) inhibitors and heart failure and have mixed results.
The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study showed that patients treated with saxagliptin (a DPP-4 inhibitor) were more likely to be hospitalized for heart failure than were those given placebo (3.5% vs. 2.8%, respectively). However, Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) and Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), recent multicenter, randomized, double-blind, non-inferiority trials, evaluated heart failure and mortality outcomes in patients with type 2 diabetes taking different DPP-4 inhibitors, alogliptin and sitagliptin, respectively, compared with placebo.
EXAMINE reported that the hospital admission rate for heart failure was 3.1% for patients randomly assigned to alogliptin compared with 2.9% for those randomly assigned to placebo (hazard ratio 1.07 [95% CI 0.79–1.46]). Alogliptin had no effect on the composite end point of cardiovascular death and hospital admission for heart failure in the post hoc analysis (hazard ratio 1.00 [95% CI 0.82–1.21]).
TECOS showed a non-significant difference in the rate of heart failure hospitalization for the sitagliptin group (3.1%; 1.07 per 100 person-years) compared with the placebo group (3.1%; 1.09 per 100 person-years).