Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory Analysis

Background In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe CKD, dulaglutide (DU) treatment slowed decline in eGFR compared with insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and BP. 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 0.75 or 1.5 mg DU weekly or IG daily as basal therapy, with titrated insulin lispro, for 1 year. The time to occurrence of the composite outcome of >= 40% eGFR decline, ESKD, or death due to kidney disease was compared using a Cox proportional-hazards model. Results Patients treated with 1.5 mg DU weekly versus IG daily for 1 year had a lower risk of >= 40% eGFR decline or ESKD events in the overall study population (5% versus 11%; hazard ratio, 0.45; 95% CI, 0.20 to 0.97; P=0.04). Most events occurred in the subset of patients with macroalbuminuria, where risk of the composite outcome was substantially lower for 1.5 mg DU versus IG (7% versus 22%; hazard ratio, 0.25; 95% CI, 0.10 to 0.68; P=0.006). No deaths due to kidney disease occurred. Conclusions Treatment with 1.5 mg DU weekly was associated with a clinically relevant risk reduction of >= 40% eGFR decline or ESKD compared with IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.