Dulaglutide and Kidney Function–Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis
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 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=4949 DU, N=4952 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 ≥30mg/g) and baseline eGFR (<60 or ≥60mL/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% Confidence Interval [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). 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.