Sitagliptin Use in Patients With Diabetes and Heart Failure: A Population-Based Retrospective Cohort Study

Study Questions:

What are the effects of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and incident heart failure (HF)?


This was a population-based, retrospective cohort study conducted with the use of a national commercially insured US claims database. Within the database, the authors identified a cohort of patients with T2DM taking metformin or a sulfonylurea and newly diagnosed HF. The primary outcome of interest was all-cause hospital admission or death. Secondary endpoints included HF-related hospital admission or all-cause death. All subjects with the primary outcome of interest were matched on age and sex with up to 10 controls with no hospital admission. Subjects using sitagliptin were compared with those not taking sitagliptin in the 90 days before the primary outcome.


Overall, 887 patients out of a total analytic sample of 7,620 patients with T2DM and incident HF (12%) were exposed to sitagliptin therapy. Median follow-up was 1.4 years. In adjusted analyses, sitagliptin users were not at an increased risk for the primary endpoint (7.1% vs. 9.2%, adjusted odds ratio [aOR], 0.84; 95% confidence interval [CI], 0.69-1.03). While those exposed to sitagliptin were generally similar to those not exposed to sitagliptin (with respect to covariates), those exposed to sitagliptin were more likely to have a history of diabetes complications or ischemic heart disease before incident HF. Sitagliptin was associated with an increased risk of HF-related hospital admission alone (12.5% vs. 9.0%, aOR, 1.84; 95% CI, 1.16-2.92).


The authors concluded that although not associated with an increased risk of all-cause hospitalizations or death, sitagliptin was associated with an increased risk of HF-related hospitalizations among those with T2DM and incident HF.


There is considerable uncertainty about the safety of sitagliptin in patients with T2DM and HF, and current guidelines from the American Diabetes Association suggest caution with the use of antihyperglycemics in patients with HF. This study adds to the mounting evidence that DPP-4 inhibitors may increase the risk of HF, challenging a platform of basic science data that DPP-4 inhibition may actually have a beneficial impact on cardiovascular function. The limitations of the study (including the imbalance in ischemic heart disease and diabetes complications in sitagliptin users vs. nonusers and a relatively small number of events) aside, the authors provide cogent evidence to continue to exercise caution with the use of sitagliptin in patients with T2DM. The results of the randomized TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) trial should help more clearly establish the impact of DPP-4 inhibitors on HF in patients with T2DM.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Demography, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Heart Failure, Hospitalization, Metformin, Pyrazines, Triazoles

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