Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

TLDR

Data are lacking on the long‑term cardiovascular effects of adding sitagliptin to usual care in type 2 diabetes patients with cardiovascular disease, prompting a randomized double‑blind study of 14,671 participants. The trial employed open‑label antihyperglycemic therapy to achieve individualized glycemic targets and tested sitagliptin’s noninferiority versus placebo using a relative risk margin of 1.3, with the primary outcome a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina hospitalization. Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (HR 0.98, 95% CI 0.88–1.09), with similar rates of heart failure, pancreatitis, and pancreatic cancer, and no significant difference in major adverse cardiovascular events. Funded by Merck Sharp & Dohme; registered as TECOS (ClinicalTrials.gov NCT00790205).

Abstract

Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease.In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32).Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.).