Sitagliptan and Heart Failure Hospitalization in Type 2 Diabetes

Study Questions:

What is the association of sitagliptin use with hospitalization for heart failure (hHF) and related outcomes?


This was a post hoc analysis of the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) trial. TECOS was a randomized, double-blind, placebo-controlled study evaluating the cardiovascular (CV) safety of sitagliptin versus placebo. Prespecified HF-related outcomes included the time to the first hHF, the time to the first event of hHF or CV death, the time to the first event of hHF or all-cause death, total hHF events (including recurrent hHF), and the time to the first hHF in subgroup analyses.


Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively. There was no significant difference for the composite of hospitalization for HF or CV death (7.3% vs. 7.2%, respectively). No heterogeneity for the effect of sitagliptan on hHF was observed in subgroup analyses across 21 factors (including those at highest risk for hHF, such as patients with previous HF).


Sitagliptan does not affect the risk for hHF in patients with type 2 diabetes mellitus (T2DM).


This is a valuable study that helps establish that the dipeptidyl peptidase 4 inhibitor (DPP4i) sitagliptan does not increase risk for hHF. This stands in contrast to the signals presented in SAVOR-TIMI 53 (saxagliptan vs. placebo) and EXAMINE (alogliptin vs. placebo in patients with recent acute coronary syndrome) trials. In SAVOR-TIMI 53, saxagliptan use was associated with an unexpected increased risk for hHF. In EXAMINE, there was a nonsignificant numerical increase of hHF associated with alogliptan use. Although it is unclear why the findings from TECOS are different from those from SAVOR-TIMI 53 and EXAMINE and even the mechanism through which DPP4is could be associated with HF is uncertain, the current post hoc analysis provides evidence that sitagliptan may be safely used in a population of patients with T2DM at escalated CV risk.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Heart Failure, Hospitalization, Hypoglycemic Agents, Risk, Secondary Prevention, Treatment Outcome

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