Linagliptin in patients with type 2 diabetes and cardiovascular and/or renal disease: results from a cardiovascular and renal outcomes trial

Review of: Rosenstock J, Perkovic V, Johansen, OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321:69-79. McGuire DK, Alexander JH, Johansen OE, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139:351-361. These two papers describe the findings from the CARMELINA trial (Cardiovascular and Renal Microvascular Outcome Study with Linagliptin): the first paper reported results for the primary cardiovascular composite outcome (cardiovascular [CV] death, nonfatal myocardial infarction [MI], or nonfatal stroke; 3-point major adverse cardiovascular event [3P-MACE]) and the key secondary renal composite outcome (renal death, end-stage kidney disease, or sustained >= 40% decrease in eGFR from baseline); the second paper reported secondary analyses of heart failure (HF) and related outcomes. The CARMELINA trial was a randomized, placebo-controlled, multicenter non-inferiority trial of adults with type 2 diabetes mellitus (T2DM) and elevated CV and renal risk. After a median 2.2-year follow-up of 6979 participants, patients allocated to linagliptin demonstrated no increase in the risk of 3P-MACE versus placebo: hazard ratio (HR) 1.02 [95% confidence interval (CI) 0.89-1.17]; P < 0.001 for non-inferiority. There was also no increase in the risk of hospitalization for HF for linagliptin versus placebo (HR 0.90 [0.74-1.08]). There was no increased risk of progression to end-stage kidney disease or death due to kidney disease (HR 0.87 [0.69-1.10]). Additionally, progression of albuminuria occurred less frequently in patients who received linagliptin versus placebo (HR 0.86 [0.78-0.95]). Overall, no new safety findings were identified for linagliptin, and no increased risk of hypoglycemia was observed for linagliptin versus placebo. Together, these findings from the CARMELINA trial reaffirm treatment guidelines for choosing additional therapies for patients with T2DM at elevated CV and/or renal risk, and provide new information on the role of linagliptin in the management of T2DM.