Results from the TECOS trial indicate patients with type 2 diabetes and cardiovascular disease treated with sitagliptin are not at higher risk for cardiovascular events or hospitalization.
The first dipeptidyl peptidase-4 (DPP-4) inhibitor was approved in 2006 and since then several studies have shown that this class of drugs may be associated with an increased risk of cardiovascular events, especially heart failure. Now, results from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) indicate that one DPP-4 inhibitor, sitagliptin, is not associated with an increased risk of cardiovascular events.
The TECOS trial was a 6-year study that evaluated cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease who were randomized to receive either sitagliptin or placebo, in addition to standard diabetes care. Rury R. Holman, FRCP, FMedSci, cochair of the TECOS executive committee, and colleagues presented the findings on June 8 at the American Diabetes Association 75th Scientific Sessions in Boston, MA.
TECOS enrolled 14,671 participants (7,332 in the sitagliptin arm and 7,339 in the placebo arm) from 38 different countries (17.7% from the US). Patients were at least 50 years old, had an HbA1c level from 6.5 to 8.0%, and had a preexisting vascular disease such as a history of myocardial infarction, coronary revascularization, or ischemic stroke. Nearly three-fourths (74%) of patients in each group had a prior cardiovascular event. Both groups had an average body mass index (BMI) of 30.2, epidermal growth factor receptor (eGFR) of 74.9, and a female population slightly above 29%. While no patients were on open-label DPP-4 inhibitors or glucagon-like peptide-1 (GLP-1) agonists, nearly 80% were also taking metformin.
Subjects with an eGFR of 50 mL/min or above were prescribed sitagliptin 100 mg/day and those with 30 to 50 mL/min received 50 mg/day. Study author Jennifer B. Green, MD, explained that patients were advised to continue any existing glucose-lowering medications unless otherwise instructed. The average total follow-up period was 5.7 years and duration of the disease did not prove to cause any differences in the data.
The authors revealed there were no significant differences between the two groups in terms of the study’s primary composite cardiovascular endpoint (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) or in the secondary endpoint of hospitalization for heart failure.
There were also no significant differences between the groups in rates of infection, severe hypoglycemia, renal failure, or cancer.
M. Angelyn Bethel, MD, another researcher on the study, said that one “statistically significant” finding showed that there was a fairly consistent eGFR drop of 1.34 mL/mill in the sitagliptin group compared to placebo.
Researchers predicted 1,300 primary events would occur; however, that number was slightly higher with cardiovascular outcomes occurring in 839 patients (11.4%) who received sitagliptin and 851 (11.6%) on placebo.
“Again, the adults are identical in [hospitalization for heart failure or cardiovascular death with] 538 sitagliptin (7.3%) and 525 patients (7.2%) in the placebo group,” Holman said.
Over the course of the trial, sitagliptin patients proved to have better glycemic control when compared to the placebo group, with a lower average by 0.29%.
“The utility of sitagliptin as a glucose-lowering agent was confirmed by the more frequent initiation of insulin therapy and the greater need for additional anti-hyperglycemic agents in the placebo group compared with the sitagliptin group,” the authors wrote.
Furthermore, 547 patients (7.5%) taking sitagliptin and 537 (7.3%) taking placebo died during TECOS — 167 on sitagliptin (2.3%) and 171 on placebo (2.3%) being non-cardiovascular deaths. Taking into the account the number of events, Holman explained that they “didn’t identify any gain or failure” with the DPP-4 inhibitor in regards to cardiovascular health.