Linagliptin and cardiorenal outcomes in Asians with type 2 diabetes mellitus and established cardiovascular and/or kidney disease: subgroup analysis of the randomized CARMELINA^® trial

Objective: Linagliptin, a dipeptidyl peptidase-4 inhibitor, demonstrated cardiovascular and renal safety in type 2 diabetes mellitus (T2DM) patients with established cardiovascular disease (CVD) with albuminuria and/or kidney disease in the multinational CARMELINA^® trial. We investigated the effects of linagliptin in Asian patients in CARMELINA^®. Methods: T2DM patients with HbA1c 6.5–10.0% and established CVD with urinary albumin-to-creatinine ratio (UACR) > 30 mg/g, and/or prevalent kidney disease (estimated glomerular filtration rate [eGFR] 15–< 45 ml/min/1.73 m² or ≥ 45–75 with UACR > 200 mg/g), were randomized to linagliptin or placebo added to usual care. The primary endpoint was time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3-point MACE). Results: Of the 6979 patients, 555 (8.0%) were Asians living in Asia. During a median follow-up of 2.2 years, 3-point MACE occurred in 29/272 (10.7%) and 33/283 (11.7%) of linagliptin and placebo patients, respectively (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.55–1.48), consistent with the overall population (HR 1.02; 95% CI 0.89–1.17; P value for treatment-by-region interaction: 0.3349). Similar neutrality in Asian patients was seen for other cardiorenal events including the secondary kidney endpoint of death from renal failure, progression to end-stage kidney disease, or ≥ 40% eGFR decrease (HR 0.96; 95% CI 0.58–1.59). Linagliptin was associated with a nominal decrease in the risk of hospitalization for heart failure (HR 0.47; 95% CI 0.24–0.95). Overall in Asian patients, linagliptin had an adverse event rate similar to placebo, consistent with the overall population. Conclusions: Linagliptin showed cardiovascular and renal safety in Asian patients with T2DM and established CVD with albuminuria and/or kidney disease.