A study evaluating the cardiovascular safety of Merck's type 2 diabetes drug sitagliptin determined the dipeptidyl peptidase-4 inhibitor does not increase the risk for heart failure hospitalization.
The largest study to date evaluating the cardiovascular safety of Merck’s type 2 diabetes drug sitagliptin (Januvia) determined the dipeptidyl peptidase-4 (DDP-4) inhibitor does not increase the risk for heart failure (HF) hospitalization.
This randomized, double-blind TECOS trial published in The New England Journal of Medicine assigned 14,671 patients with diabetes and cardiovascular disease (CVD) to add either daily sitagliptin 100 mg or placebo to their existing diabetes therapy. Patients with normal cardiovascular function or previous use of DDP-4 inhibitors were not eligible to participate.
The primary outcomes were cardiovascular death, nonfatal myocardial infarction (MI) or stroke, or hospitalization for unstable angina. Secondary outcomes included hospitalizations for HF and death from any cause.
After 3 years of follow-up, there was no difference between sitagliptin and placebo on any outcomes. Death, MI, unstable angina, and stroke occurred in 11.4% of the sitagliptin population compared with 11.6% of the placebo participants, and both groups had the same hospitalization rates for HF (3.1%). They also had similar rates of infection, cancer, site-reported renal failure, and severe hypoglycemia.
This study is an important vindicator for sitagliptin because previous—albeit less robust—studies implied that DDP-4 inhibitors may worsen HF.
In 2014, researchers analyzed insurance claims from 7620 individuals with HF and diabetes, and they found sitagliptin increased the risk of HF-related hospitalization by 84%. However, the researchers stressed that causal inferences could not be made because the study was observational.
In the previous year, researchers from Harvard Medical School conducted a larger study of a related DDP-4 inhibitor, saxagliptin (Onglyza), which randomly assigned 16,492 patients with diabetes and CVD to receive either saxagliptin or placebo. The saxagliptin group had a 27% higher risk of hospitalization for HF, which prompted the FDA to investigate the drug’s safety. The FDA concluded in April that saxagliptin must carry stronger warnings on its label.
Now, however, pharmacists can rest assured that sitagliptin is safe for use in type 2 diabetics with CVD.