Cardiovascular and renal outcomes by baseline albuminuria status and renal function - results from the LEADER randomized trial

AIM: To assess cardiorenal outcomes by baseline urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in the contemporary LEADER cohort.

MATERIALS AND METHODS: LEADER was a multinational, double-blind trial. Patients with type 2 diabetes and high cardiovascular (CV) risk were randomized 1:1 to the glucagon-like peptide-1 analogue liraglutide (≤1.8 mg daily; n = 4668) or placebo (n = 4672) plus standard care and followed for 3.5 to 5 years. Primary composite outcomes were time to first non-fatal myocardial infarction, non-fatal stroke or CV death. Post hoc Cox regression analyses of outcomes by baseline UACR and eGFR subgroups were conducted with adjustment for baseline variables.

RESULTS: In the LEADER population, 1598 (17.5%), 2917 (31.9%), 1200 (13.1%), 1611 (17.6%), 845 (9.2%) and 966 (10.6%) had UACR = 0, >0 to <15, 15 to <30, 30 to <100, 100 to <300 and ≥300 mg/g, respectively. Increasing UACR and decreasing eGFR were linked with higher risks of the primary outcome, heart failure hospitalization, a composite renal outcome and death (P-values for the Cochran-Armitage test for trends were all <.0001). Across UACR and eGFR subgroups, risks of cardiorenal events and death were generally lower or similar with liraglutide versus placebo.

CONCLUSIONS: In a contemporary type 2 diabetes population, increasing baseline UACR and declining eGFR were linked with higher risks of cardiorenal events and death.