There is some uncertainty in the literature about whether DPP-4 inhibitors are harmful to diabetic patients with heart failure….
DPP-4 inhibitors have recently been shown to improve cardiovascular risk factors, including LDL, HDL and blood pressure. However there is controversy around the safety of patients with existing heart failure. Therefore, a population-based, retrospective cohort study was performed using a large United States claims database including individuals from all 50 states to evaluate the effects of sitagliptin, the most widely used DPP-4 inhibitor in North America, in patients with type 2 diabetes and heart failure.
Individuals who had prescription claims for metformin or a sulfonlyurea from January 1, 2003 to December 31, 2009 and who subsequently developed heart failure were identified. A total of 7,620 patients met inclusion criteria. Overall, 887 patients (12%) were exposed to sitagliptin therapy after incident heart failure. Subjects were followed from the date of incident heart failure until death, termination of insurance policy, or December 31, 2010.
The primary outcome being measured was "all-cause hospital admission or death" and secondary endpoints including heart failure related hospital admissions or all-cause death. A nested case control approach was used to evaluate the effects of sitagliptin treatment. Subjects using sitagliptin were compared with those not using sitagliptin in the 90 days before primary outcome of all cause hospital admission or death occurred.
Of the 7,620 patients included in the study, the primary endpoint occurred in 4,137 patients (54%); 4,076 patients were admitted to the hospital at least once (824 for heart failure) and 408 patients (5.4% died). Upon complete analysis, sitagliptin users were not shown to be at an increased risk for the primary endpoint of all cause hospitalizations or death (7.1% vs. 9.2%); adjusted odds ratio was 0.84 using a 95% confidence interval. However, sitagliptin was associated with an increased risk of heart failure associated hospitalizations (12.5% vs 9.0%; odds ratio 1.84).
The increase in heart failure events with sitagliptin use is likely clinically relevant, resulting in a number needed to harm of 29, and may have implications for choice of add-on therapy for patients with heart failure and diabetes.
- DPP-4 inhibitors have recently been shown to improve cardiovascular risk factors, including LDL, HDL and blood pressure
- Sitagliptin users were not shown to be at an increased risk for the primary endpoint of all cause hospitalizations or death (7.1% vs. 9.2%)
- Sitagliptin was associated with an increased risk of heart failure associated hospitalizations (12.5% vs 9.0%)
Weir, Daniala L., McAlister, Finlay MD., Senthilselvan, Ambikaipakan PhD, et al. Sitagliptin Use in Patients with Diabetes and Heart Failure: A Population-Based Retrospective Cohort Study. JACC: Heart Failure. June 25, 2014.