Kidney Week

Abstract: TH-OR033

CKD Outcomes in Type 2 Diabetes and Moderate-to-Severe CKD Treated with Dulaglutide Versus Insulin Glargine: AWARD-7

Session Information

• Diabetic Kidney Disease Trials: Progress Being Made
  October 25, 2018 | Location: 5A, San Diego Convention Center
  Abstract Time: 04:54 PM - 05:06 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Tuttle, Katherine R., University of Washington School of Medicine, Spokane, Washington, United States

Katherine R. Tuttle, MD, FASN



Katherine R. Tuttle, MD, FASN, FACP, FNKF, is the regional Principal Investigator for the Institute of Translational Health Sciences, Investigator at the Kidney Research Institute, and Professor of Medicine in the Nephrology Division at the University of Washington and Executive Director for Research at Providence Health Care. Dr. Tuttle’s major research interests are in the areas of clinical and translational science and precision medicine strategies to tackle diabetic kidney disease and other chronic kidney diseases.

• Lakshmanan, Mark, Eli Lilly and Company, Indianapolis, Indiana, United States

Mark Lakshmanan,

• Rayner, Brian, Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

Brian Rayner,

• Zimmermann, Alan G., Formerly at Eli Lilly and Company, Indianapolis, Indiana, United States

Alan G. Zimmermann,

• Woodward, Brad, Eli Lilly and Company, Indianapolis, Indiana, United States

Brad Woodward,

• Botros, Fady T., Eli Lilly and Company, Indianapolis, Indiana, United States

Fady T. Botros,

Background

In the Assessment of Weekly AdministRation of Dulaglutide in Diabetes-7 (AWARD-7) study, dulaglutide (DU) treatment was associated with slower decline in estimated glomerular filtration rate (eGFR) compared to insulin glargine (IG) in participants with type 2 diabetes (T2D) and moderate-to-severe chronic kidney disease (CKD). The present analysis is aimed to determine CKD outcomes by treatment group.

Methods

As treatment for T2D, participants with T2D and CKD stages 3-4 were randomized (1:1:1) to receive DU 0.75 mg, DU 1.5 mg, or titrated IG, all added-on to titrated insulin lispro, for 1 year in this open-label (DU dose-blinded), phase 3 clinical study. In this prespecified exploratory analyses, proportions of participants experiencing ≥40% eGFR decline, end-stage renal disease (ESRD), or kidney disease-related death were compared between groups as composite and individual outcomes. For the composite outcome, a time-to-event analysis was conducted using a Cox proportional hazards model.

Results

The age (mean ± SD) of participants was 64.5 ± 8.5 years and 264/549 (48%) were women. At baseline, diabetes duration (mean ± SD) was 18.1 ± 8.8 years, HbA1c was 8.6 ± 1.0%, eGFR was 38 ± 13 mL/min/1.73 m², and median (interquartile range) urine albumin-creatinine ratio was 209 (39, 965) mg/g. HbA1c declined similarly in all groups by a mean of approximately 1% over 1 year. The composite outcome was experienced by 47/576 (8.2%) participants: 10/192 (5.2%) in DU 1.5 mg, 16/190 (8.4%) in DU 0.75 mg, and 21/194 (10.8%) in IG (p=0.046, p=0.548 versus IG, respectively).The time-to-event for the composite outcome was significantly better for DU 1.5 mg versus IG (Cox model; p=0.038). Proportions with eGFR decline ≥40% occurred in: 2/192 (1.0%) in DU 1.5 mg, 7/190 (3.7%) in DU 0.75 mg, and 6/194 (3.1%) in IG. Proportions reaching ESRD were: 8/187 (4.3%) in DU 1.5 mg, 14/184 (7.6%) in DU 0.75 mg, and 16/191 (8.4%) in IG. Between-group comparisons were not significant for individual outcomes. No kidney disease-related deaths were reported.

Conclusion

One-year treatment with DU 1.5 mg was associated with a lower rate of CKD outcomes, including the composite outcome of eGFR decline ≥40% or ESRD, compared to IG at similar levels of glycemic control.

Funding

• Commercial Support – Eli Lilly and Company