Sitagliptin may be associated with more heart failure-related hospitalizations

Sitagliptin was associated with an increased risk of heart failure hospitalizations in patients with diabetes and preexisting heart failure, a study found.

Researchers conducted a population-based, retrospective cohort study from a national database of commercially insured patients from all 50 states. Patients in the cohort had a prescription claim for metformin or sulfonylurea from January 2003 through December 2009 and subsequently developed heart failure. Patients taking sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, were compared with patients not on the drug.

The researchers examined a composite endpoint of all-cause hospital admission or death with secondary endpoints including heart failure-related hospital admission or all-cause death. Results appeared in JACC: Heart Failure on July 2.

Among 7,620 patients with diabetes and incident heart failure, the mean age was 54 years and 58% were men. Overall, 887 patients (12%) used sitagliptin (521 patient-years of exposure) after heart failure. The primary composite endpoint occurred in 4,137 patients (54%); 4,076 patients (53.5%) were admitted to the hospital at least once (824 for heart failure); and 408 patients (5.4%) died. The secondary endpoint of heart failure-related hospital admission or all-cause death occurred in 1,146 patients (15.0%).

After adjustment, sitagliptin users had a statistically insignificant difference in risk of the combined endpoint of admission or death (7.1% vs. 9.2%; adjusted odds ratio [aOR], 0.84; 95% CI, 0.69 to 1.03). The groups were also similar in their risk for those endpoints individually (hospital admission, 7.5% vs. 9.2%; aOR, 0.93; 95% CI, 0.76 to 1.14; death, 6.9% vs. 9.3%; aOR, 1.16; 95% CI, 0.68 to 1.97).

When heart failure-related events were examined specifically, sitagliptin was not associated with an increased risk of combined heart failure-related hospital admission or death (9.0% vs. 9.1%; aOR, 1.34; 95% CI, 0.93 to 1.92). However, it was associated with an increased risk of heart failure-related hospital admission alone (12.5% vs. 9.0%; aOR, 1.84; 95% CI, 1.16 to 2.92).

The authors concluded, “The increase in heart failure events is likely clinically relevant (resulting in a number need to harm of 29) and may have implications for choice of add-on therapy for patients with heart failure and diabetes poorly controlled with other agents.”

An accompanying editorial cited several other trials that suggest associations of diabetes medications with heart failure. “With these considerations in mind, the present findings are important and do add to a small but growing body of evidence that suggests DPP-4 inhibitors as a class of drugs, and possibly diabetes drugs in general, may increase the risk of heart failure,” the editorial stated. “This increase in absolute risk, if present at all, appears to be small.”