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).


Continue Reading

Regarding safety, the linagliptin profile was consistent with previous data and no new safety signals were reported.

Related Articles

“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.

For more information visit boehringer-ingelheim.com or lilly.com.