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Sitagliptin may increase hospitalizations in patients with diabetes, HF
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Recent study results found that sitagliptin use by patients with type 2 diabetes and HF may increase the risk for HF-related hospitalization.
Sitagliptin (Januvia, Merck) is a dipeptidyl-peptidase IV (DPP-IV) inhibitor, a class of drug whose safety has been debated in patients with diabetes and HF.
Researchers conducted a retrospective cohort study using data from a national commercially insured US claims database (Clinformatics Data Mart, OptumInsight Life Sciences Inc.) to evaluate the effects of sitagliptin in patients with type 2 diabetes and HF. They analyzed patients who had a prescription claim for metformin or a sulfonylurea from 2003 to 2009 and subsequently developed incident HF (n=7,620; mean age, 54 years; 58% men).
The primary outcome was a composite of death and all-cause hospital admission. The researchers also analyzed those two outcomes separately, as well as HF-specific hospitalization or mortality. They compared sitagliptin users vs. nonusers via a nested case-control analysis after adjustment for demographics and clinical and laboratory data.
Signal for HF
Twelve percent of patients used sitagliptin after incident HF. The primary composite outcome was reported in 54%. Patients who used sitagliptin were not at elevated risk for the primary endpoint (users, 7.1%; nonusers, 9.2%; adjusted OR=0.84; 95% CI, 0.69-1.03), for all-cause hospital admission (users, 7.5%; nonusers, 9.2%; adjusted OR=0.93; 95% CI, 0.76-1.14) or all-cause mortality (users, 6.9%; nonusers, 9.3%; adjusted OR=1.16; 95% CI, 0.68-1.97).
However, sitagliptin use was associated with increased risk for HF hospitalization (users, 12.5%; nonusers, 9%; adjusted OR=1.84; 95% CI, 1.16-2.92; number needed to harm=29).
“The increase in HF events is likely clinically relevant … and may have implications for choice of add-on therapy for patients with HF and diabetes poorly controlled with other agents,” Daniala L. Weir, BSc, from the University of Alberta in Canada, and colleagues wrote. “Although our results are intriguing, it is clear that additional studies are required, specifically in patients with HF, to solidify the risk-benefit picture.”
In addition, Weir and colleagues wrote, “although this was a rigorous observational study, we must still be cautious in our interpretations and conclusions because causal inferences cannot be made on the basis of observational studies alone. Despite the use of propensity scores, confounding by indication may still introduce bias. Indeed, patients at risk for HF or with asymptomatic left ventricular dysfunction will be potentially less likely to be prescribed other drugs that may make HF worse according to clinical judgment.”
The Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, which is underway, may shed some more light on the issue, they noted.
Evidence growing
Deepak L. Bhatt
In an invited commentary, Deepak L. Bhatt, MD, MPH, and Matthew A. Cavender, MD, MPH, both from Brigham and Women’s Hospital and Harvard Medical School, wrote, “The present findings are important and do add to a small but growing body of evidence that suggests DPP-IV inhibitors as a class of drugs, and possibly diabetes drugs in general, may increase the risk [for HF].”
Bhatt, the chief medical editor of Cardiology Today’s Intervention, and Cavender noted that “basic science and epidemiological studies are needed to explore these potential associations and identify mechanisms though which antihyperglycemic agents might cause [HF]. The findings of this analysis, as well as other recent studies, highlight the need for well-designed trials that rigorously assess for [HF] in patients with diabetes.”
In the meantime, they wrote, patients with diabetes and pre-existing HF should be followed closely as outpatients for signs and symptoms of HF if they are started on a DPP-IV inhibitor or perhaps even any diabetes medication.
For more information:
Bhatt DL. JACC Heart Fail. 2014;doi:10.1016/j.jchf.2014.05.005.
Weir DL. JACC Heart Fail. 2014;doi:10.1016/j.jchf.2014.04.005.
Disclosure: Several researchers report being employed or supported by Alberta Innovates Health Solutions and the Canadian Institutes of Health Research. See the full editorial for Bhatt’s and Cavender’s relevant financial disclosures.