Boehringer Ingelheim and Lilly announced full data from the CAROLINA trial demonstrating that linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, did not increase cardiovascular (CV) risk compared with glimepiride, a sulfonylurea, in adults with type 2 diabetes and CV risk.
The multinational, randomized, double-blind, active-controlled CAROLINA (CARdiovascular Outcome study of LINAgliptin versus glimepiride in patients with type 2 diabetes) trial (N=6033) evaluated the CV safety of linagliptin (5mg once daily) vs glimepiride, in addition to standard of care, in adults with type 2 diabetes at increased CV risk or those with established CV disease; median follow-up was over 6 years. Study patients had early type 2 diabetes (median disease duration of 6.2 years) and were either treatment-naive or received 1-2 glucose-lowering agents.
Results showed non-inferiority for linagliptin vs glimepiride in meeting its primary endpoint of time to first occurrence of CV death, non-fatal myocardial infarction or non-fatal stroke (3P-MACE), which occurred in 11.8% and 12.0% of patients, respectively. A similar outcome between treatment groups was noted for the secondary endpoint of 3P-MACE plus hospitalization for unstable angina (4P-MACE; 13.2% for linagliptin vs 13.3% for glimepiride).
Moreover, a higher proportion of the linagliptin group (16.0%) achieved treatment sustainability (secondary composite efficacy endpoint defined as A1C ≤7% at the final visit without rescue medication, without any moderate or severe hypoglycemia episodes and without a ≥2% weight gain) compared with glimepiride (10.2%). While both treatments had a similar effect on A1C, fewer patients in the linagliptin group experienced a hypoglycemic event compared with the glimepiride group (10.6% vs 37.7%, respectively).
Regarding safety, the linagliptin profile was consistent with previous data and no new safety signals were reported.
“The findings from CAROLINA complement the results from CARMELINA, which demonstrated similar long-term cardiovascular safety for [linagliptin] compared with placebo, including no increased risk of hospitalization for heart failure, in adults with type 2 diabetes at high risk for cardiovascular and kidney disease,” said Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development & Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.
Linagliptin is marketed under the brand name Tradjenta and is currently FDA-approved as an adjunct to diet and exercise in type 2 diabetes, as monotherapy or combination therapy.