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Januvia for High Risk CVD Patients is Safe

May 14, 2016

A secondary analysis of the TECOS trial affirms sitagliptin does not increase heart failure risk for patients with type 2 diabetes.

Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP-4) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP-4 inhibitor sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS).


The secondary analysis was conducted to assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes.

TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14,671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015.

Patients were randomized to sitagliptin vs placebo added to standard care. Pre-specified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death.

Based on the results from 14,671 patients, 7,332 were randomized to sitagliptin and 7,339 to placebo and showed that hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively. There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P >  .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16).

The results of the present analyses demonstrate that sitagliptin use did not affect the risk for hHF or related adverse clinical outcomes, overall or across selected subgroups of interest. In the context of the primary findings from TECOS that demonstrated noninferiority of the effects of sitagliptin vs placebo on major atherosclerotic adverse CV events, the present results provide further support that sitagliptin may be safely used in a population of patients with T2DM at high CV risk.

Practice Pearls:

  • This randomized, placebo-controlled clinical trial included 14,671 adults with type 2 diabetes mellitus and prevalent atherosclerotic vascular disease.
  • In secondary analyses, over a median follow-up of 2.9 years, there were no significant differences between sitagliptin vs placebo for the risk of hospitalization for heart failure (3.1% vs 3.1%, respectively) or for the composite of hospitalization for heart failure or cardiovascular death (7.3% vs 7.2%, respectively).
  • Sitagliptin use has a neutral effect on hospitalization for heart failure risk in patients with type 2 diabetes mellitus at high cardiovascular risk.

McGuire DK, et al. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.0103; ENDO 2016: The Endocrine Society Annual Meeting