Dulaglutide in Diabetes and Chronic Kidney Disease: AWARD-7 Exploratory Analysis of Clinical Outcomes

Background: In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe chronic kidney disease (CKD), dulaglutide (DU) treatment slowed decline in estimated glomerular filtration rate (eGFR) compared to insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and blood pressure. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups. Methods: Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to DU 0.75 mg or 1.5 mg weekly or IG daily as basal therapy, with titrated insulin lispro, for one year. The time to occurrence of the composite outcome of ≥40% eGFR decline, end-stage kidney disease (ESKD), or death due to kidney disease was compared using a Cox proportional hazards model. Results: Patients treated with DU 1.5 mg weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5.2% versus 10.8%; hazard ratio 0.45, 95% confidence interval 0.20-0.97, P=0.042). Most events occurred in the subset with macroalbuminuria, where risk of the composite outcome was substantially lower for DU 1.5 mg versus IG (7.1% versus 22.2%; hazard ratio 0.25, 95% confidence interval 0.10-0.68, P=0.006). No deaths occurred. Conclusions: Treatment with DU 1.5 mg weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared to IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD