P6272First plus recurrent CV and hospitalization events in the CArdiovascular and Renal Microvascular outcomE study with LINAgliptin (CARMELINA) in patients with type 2 diabetes and cardiorenal disease

Background/Introduction CARMELINA was a randomized placebo-controlled clinical trial designed to demonstrate the cardiovascular (CV) safety of linagliptin in patients with type 2 diabetes (T2D) and concomitant cardiorenal disease. Despite a particularly elevated CV risk, only limited long-term evidence from randomized controlled trials for safety and efficacy of glucose lowering medications is available for this population. Purpose To characterize the effects of linagliptin on net CV disease and hospitalization burden in this population. Methods People with T2D and either i) urine albumin creatinine ratio (UACR) >30 mg/g with concomitant CV disease, or ii) estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 regardless of UACR, or eGFR ≥45–75 mL/min/1.73m2 and UACR >200 mg/g, were randomized to linagliptin 5 mg or placebo q.d. in a double-blind fashion in addition to standard of care. We assessed the effects of linagliptin versus placebo on all first plus recurrent CV events and all-cause hospitalizations using a using a negative binomial model to account for within-subject correlation. Results A total of 6979 participants were enrolled (mean age 66 years, 63% male, eGFR 54.6 ml/min/1.73m2, median UACR 162 mg/g, 59% with history of ischemic heart disease, 27% with history of heart failure (HF)) and followed for a median of 2.2 years. Adding recurrent events increased the number of events for analysis from 5.3–57.5% across CV/HF outcomes and 112.4% for hospitalizations. In analyses of first plus recurrent events, the event rate ratio (95% CI) with linagliptin versus placebo was 0.98 (0.82, 1.16; p=0.78) for 3-point MACE, 1.03 (0.79, 1.35; p=0.83) for myocardial infarction 1.03 (0.83, 1.29; p=0.77) for myocardial infarction plus revascularization, 0.89 (0.65, 1.22; p=0.48) for stroke, 0.94 (0.70, 1.27; p=0.69) for stroke plus TIA, 0.94 (0.75, 1.20; p=0.63) for hospitalized HF, 0.92 (0.77, 1.11; p=0.40) for the composite of CV death or hospitalized HF, and 0.96 (0.87, 1.06; p=0.40) for all-cause hospitalization (Figure). Conclusion Linagliptin showed similar risk of either first or recurrent CV or hospitalization events compared with placebo in patients with T2D and cardiorenal disease. These data support the CV safety of linagliptin and, considering the high volume of recurrent events, underscores the significant CV disease burden experienced by patients with T2D and cardiorenal disease Acknowledgement/Funding Boehringer Ingelheim and Eli Lilly