Cardiovascular and kidney outcomes of linagliptin treatment in older people with type 2 diabetes and established cardiovascular disease and/or kidney disease: A prespecified subgroup analysis of the randomized, placebo‐controlled CARMELINA® trial

Abstract Aims In CARMELINA®, linagliptin demonstrated cardiovascular and renal safety in patients with type 2 diabetes (T2D) with high renal and cardiovascular disease (CVD) risk. We investigated safety and efficacy of this dipeptidyl peptidase‐4 inhibitor in older participants. Materials and methods Subjects aged ≥18 years with T2D and established CVD with urinary albumin‐to‐creatinine ratio (UACR) >30 mg/g, and/or prevalent kidney disease, were randomized to linagliptin or placebo added to usual care. The primary endpoint (time to first occurrence of 3P‐MACE: cardiovascular death, non‐fatal myocardial infarction or non‐fatal stroke) and other outcomes were evaluated across age groups <65 (n = 2968), 65 to <75 (n = 2800) and ≥75 years (n = 1211). Results Mean age was 65.9 years (17.4% and 5.9% aged ≥75 and 80, respectively) and median follow‐up was 2.2 years. The hazard ratio (HR) for 3P‐MACE with linagliptin versus placebo was 1.02 [95% confidence interval (CI) 0.89, 1.17] with no significant interaction between age and treatment effect ( P = 0.0937). HRs for participants aged <65, 65 to <75 and ≥75 years were 1.11 (95% CI 0.89, 1.40), 1.09 (0.89, 1.33) and 0.76 (0.57, 1.02), respectively. Linagliptin did not increase the risk of adverse kidney outcomes or hospitalization for heart failure across age groups. The incidence of adverse events, including hypoglycaemia, increased with age but was similar with linagliptin and placebo despite glycated haemoglobin A1c reduction with linagliptin. Conclusions Linagliptin did not increase risk for cardiovascular events or hypoglycaemia and kidney function remained stable in older people with T2D and established CVD with albuminuria and/or kidney disease.