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

Abstract

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®. T2DM patients with HbA1c 6.5–10.0% and established CVD with urinary albumin-to-creatinine ratio (UACR)\u2009>\u200930 mg/g, and/or prevalent kidney disease (estimated glomerular filtration rate [eGFR] 15–<\u200945 ml/min/1.73 m2 or ≥\u200945–75 with UACR >\u2009200 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). 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\u2009≥\u200940% 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. Linagliptin showed cardiovascular and renal safety in Asian patients with T2DM and established CVD with albuminuria and/or kidney disease.