Chicago—Patients with type 2 diabetes who took linagliptin were not at higher risk of having cardiovascular events compared with patients who took other drugs, according to an analysis of 19 multicenter, randomized, double-blind, parallel group studies.
Odd Erik Johansen, MD, the study’s lead author, presented the results at the ADA meeting in an oral abstract session. Boehringer Ingelheim, manufacturer of linagliptin, funded the study.
Dr. Johansen, who is an employee of Boehringer Ingelheim, said the 9569 patients evaluated in the study were a diverse group in terms of low to high risk of having cardiovascular complications and being treatment naïve or taking concomitant treatments.
Independent of other risk factors, patients with type 2 diabetes are at least twice as much risk to have a wide range of vascular diseases such as myocardial infarction, according to Dr. Johansen. He mentioned that patients with type 2 diabetes and those with a history of coronary heart disease are in the same risk category of having cardiovascular disease. He added that more patients with type 2 diabetes are having cardiovascular problems, and they are occurring earlier in life and are more advanced at the time of diagnosis.
Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was approved by the FDA in 2011 to treat patients with type 2 diabetes. The recommended dose of linagliptin is 5 mg taken orally once daily with or without food. Dr. Johansen said studies have shown that DPP-4 inhibitors have nonglycemic cardiovascular benefits, including a decrease in blood pressure, triglycerides, and myocardial infarction size.
In this analysis, Dr. Johansen and his coauthors examined 19 trials that Boehringer Ingelheim conducted in which patients were randomized to receive linagliptin (n=5847) or a comparison drug (n=3612) for at least 12 weeks and up to 2 years. The groups were well balanced. Approximately 55% of patients were men, mean age was 58 years, and mean body mass index was 29 kg/m2.
The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina pectoris. The incidence rate of the primary end point was 13.4 per 1000 person-years in the linagliptin group and 18.9 per 1000 person-years in the other group (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.55-1.12). The combined rate of cardiovascular death, stroke, or myocardial infarction was lower in the linagliptin group compared with the other group, as well (HR, 0.74; 95% CI, 0.49-1.13).
Cardiovascular deaths were found in 0.2% of patients in each group. Nonfatal myocardial infarction was found in 0.4% of patients in the linagliptin group and 0.6% of patients in the other group, while the rates of nonfatal stroke were 0.2% and 0.5%, respectively.
Boehringer Ingelheim will further evaluate the cardiovascular safety of linagliptin in 2 additional trials, according to Dr. Johansen. The CARMELINA (Cardiovascular Safety with Linagliptin in Patients with Type 2 Diabetes Mellitus: A Pre-Specified, Prospective, and Adjudicated Meta-Analysis of a Phase 3 Program) study is a cardiovascular and renal outcomes trial with 8300 patients. The CAROLINA (Cardiovascular Outcome Study of Lingagliptin Versus Glimepiride in Patients with Type 2 Diabetes) study is a cardiovascular outcomes study comparing linagliptin with sulfonylurea glimepiride and enrolling 6103 patients.