A multi-center, international trial found that type 2 diabetes (T2D) medications linagliptin and glimepiride have similar safety profiles among patients at high-risk for cardiovascular outcomes. The findings were presented at the American Diabetes Association’s (ADA’s) 79th Scientific Sessions in San Francisco.
The CAROLINA trial took place between 2010 and 2018 and included 6,033 T2D patients (age range, 40 to 85 years; median disease duration, 6.2 years) from more than 600 sites in 43 countries. All patients had established cardiovascular disease (CVD) or had a high risk of CVD. Patients were randomized to receive, in addition to their usual treatment, a 5 mg daily dose of linagliptin or a daily dose of up to 4 mg of glimepiride. The primary outcome was a composite of cardiovascular (CV) death, non-fatal myocardial infarction, or non-fatal stroke.
The analysis included 3,020 patients taking linagliptin and 3,010 taking glimepiride. After a median follow-up of 6.3 years, the hazard ratio (HR) for the primary outcome between the linagliptin and glimepiride groups was 0.98; the HRs for CV mortality and non-CV mortality were 1.00 and 0.82, respectively. HbA1c did not significantly differ between the two groups. In the linagliptin group, 10.6% of patients experienced at least one hypoglycemia episode, compared to 37.7% in the glimepiride group. Weight differed between the groups, with the linagliptin cohort weighing an average 1.5 kg less than the glimepiride group.
The results—that CV outcomes did not differ between the two groups—surprised the researchers, according to Julio Rosenstock, MD, trial principal investigator and director of the Dallas Diabetes Research Center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, Texas.
“However, with a significantly higher risk of hypoglycemia and a modest, but statistically significant, weight gain with glimepiride compared with linagliptin, results from the CAROLINA trial confirm an important, clinically-relevant safety advantage of linagliptin over glimepiride that should be considered in the decision-making process for selecting therapy in addition to cost considerations,” Dr. Rosenstock said in a press release.