Comparable CV safety for DPP-4 inhibitor and sulfonylurea in T2DM patients with CVD or high CV risk
Comparison of DPP-4 inhibitor linagliptin with sulfonylurea glimepiride in T2DM patients with elevated risk CVD or established CVD in the CAROLINA trial (CARdiovascular Outcome study of LINAgliptin versus glimepiride in patients with type 2 diabetes) demonstrated similar impact on CV events.
The CAROLINA trial (2010-2018) was an active-comparator trial evaluating the CV effects of two commonly used diabetes medications in T2DM patients. In this double-blind, randomized trial patients were randomized to receive linagliptin or glimepiride in addition to standard therapy of metformin or other medications. Non-inferiority testing was performed in terms of occurrence of CV events. In total 6033 patients were included from >600 sites in 43 countries. Patients were between 40-85 years old, had a median diabetes duration of 6.2 years, and an increased risk of CVD or established CVD. Median follow-up was 6.3 years.
There was no difference in the primary outcome of MACE, a composite of CV death, non-fatal MI, non-fatal stroke between patients receiving linagliptin (n=3023) and those receiving glimepiride (n=3010) (HR 0.98, 95%CI: 0.84-1.14) and no difference in secondary outcomes of CV mortality and non-CV mortality (HR 1.00, 95%CI: 0.81-1.24 and HR 0.82, 95%CI: 0.66-1.03, respectively).
HbA1c was not different between the 2 groups, but weight reduction was larger in the linagliptin group vs. the glimepiride group (between-group difference in weight was -1.5 kg, 95%CI: -1.8 to -1.3). Hypoglycemia occurred less often in the linagliptin group compared to the glimepiride group (37.7% vs. 10.6% of ≥ 1 investigator-reported episode of hypoglycemia, HR 0.23, 95%CI: 0.21-0.26).