Dulaglutide and Kidney Function–Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis

Abstract

OBJECTIVE: Dulaglutide (DU) 1.5 mg was associated with improved composite renal outcomes that included new-onset macroalbuminuria in people with type 2 diabetes with previous cardiovascular disease or cardiovascular risk factors in the REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes) trial. This exploratory post hoc analysis evaluated kidney function–related outcomes, excluding the new-onset macroalbuminuria component, among the REWIND participants. RESEARCH DESIGN AND METHODS: Intent-to-treat analyses were performed on REWIND participants (n = 4,949 DU, n = 4,952 placebo). Time to occurrence of a composite kidney function–related outcome (≥40% sustained decline in estimated glomerular filtration rate [eGFR], per the Chronic Kidney Disease Epidemiology Collaboration 2009 equation, end-stage renal disease, or renal-related death), and mean annual eGFR slope were examined. Analyses were conducted overall and within subgroups defined by baseline urinary albumin-to-creatinine ratio (UACR <30 or ≥30 mg/g) and baseline eGFR (<60 or ≥60 mL/min/1.73 m2). RESULTS: The post hoc composite kidney function–related outcome occurred less frequently among participants assigned to DU than placebo (hazard ratio [HR] 0.75, 95% CI 0.62–0.92, P = 0.004), with no evidence of a differential DU treatment effect by UACR or eGFR subgroup. A ≥40% sustained eGFR decline occurred less frequently among participants assigned to DU than placebo (HR 0.72, 95% CI 0.58–0.88, P = 0.002). The mean annual decline in eGFR slope was significantly smaller for participants assigned to DU than placebo (−1.37 vs. −1.56 mL/min/1.73 m2/year, P < 0.001); results were similar for all subgroups. CONCLUSIONS: The estimated 25% reduced hazard of a kidney function–related outcome among participants assigned to DU highlights its potential for delaying or slowing the development of diabetic kidney disease in people with type 2 diabetes.