Abstract: SA-OR081
Clinical Events in Type 2 Diabetes and Moderate-to-Severe CKD by Albuminuria Status: Dulaglutide vs. Insulin Glargine
Session Information
- Moving the Needle for Treatment of Diabetic Kidney Disease
November 09, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
Abstract Time: 05:06 PM - 05:18 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Tuttle, Katherine R., University of Washington School of Medicine, Spokane, Washington, United States
- Rayner, Brian, Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa
- Lakshmanan, Mark, Eli Lilly and Company, Indianapolis, Indiana, United States
- Woodward, Brad, Eli Lilly and Company, Indianapolis, Indiana, United States
- Kwan, Anita, Eli Lilly and Company, Indianapolis, Indiana, United States
- Konig, Manige, Eli Lilly and Company, Indianapolis, Indiana, United States
- Botros, Fady T., Eli Lilly and Company, Indianapolis, Indiana, United States
Background
In participants with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD), in the AWARD-7 trial, treatment with dulaglutide (DU) compared to insulin glargine (IG) led to slower estimated glomerular filtration rate (eGFR) decline at similar levels of glycemic control and blood pressure.
Methods
To determine risk of a composite endpoint of ≥40% eGFR decline or end-stage kidney disease (ESKD) by albuminuria status, this post hoc analysis used Cox proportional hazards modeling for time to first event. Participants were randomized (1:1:1) to DU 0.75 mg or 1.5 mg weekly versus titrated IG daily for one year. eGFR was calculated using the CKD-epidemiology (EPI) creatinine and cystatin C equations.
Results
At baseline, treatment groups had similar eGFR within albuminuria subgroups (Table). Through the 1-year treatment period, the majority of events occurred in patients with macroalbuminuria; the incidence rate of the composite endpoint was significantly lower for DU 1.5 mg compared to IG in those with macroalbuminuria (Table). Consistent results were obtained when eGFR was calculated using either CKD-EPI creatinine or cystatin C equations.
Conclusion
The risk of the composite endpoint of ≥40% eGFR decline or ESKD was lower by approximately half for DU 1.5 mg compared to IG, which was mainly driven by effects in participants with macroalbuminuria.
| Baseline Characteristics (mean±SD) | Dulaglutide 1.5 mg N=192 | Dulaglutide 0.75 mg N=190 | Insulin glargine N=194 | |||
| eGFR (mL/min/1.73m2)a UACR <30 UACR 30-300 UACR >300 | 38.1±13.2 43.8±13.0 40.2±12.6 34.0±12.8 | 38.3±12.3 44.2±9.0 38.9±12.5 35.0±12.6 | 38.5±13.0 42.9±12.5 42.0±11.8 33.9±12.6 | |||
| ≥40% eGFR decline or ESKD events (a. CKD-EPI creatinine; b. CKD-EPI cystatin C) | n/N (%) | HR (95%CI) | n/N (%) | HR (95%CI) | n/N (%) | |
| Overall | a. | 10/192 (5.2) | 0.45 (0.20, 0.97)* | 16/190 (8.4) | 0.79 (0.41, 1.51) | 21/194 (10.8) |
| b. | 11/192 (5.7) | 0.49 (0.23, 1.04) | 15/190 (7.9) | 0.73 (0.38, 1.42) | 21/194 (10.8) | |
| Normal UACR <30 mg/g | a. | 2/34 (5.9) | NA | 0/44 (0.0) | NA | 0/48 (0.0) |
| b. | 3/34 (8.8) | NA | 0/44 (0.0) | NA | 1/48 (2.1) | |
| Microalbuminuria UACR 30-300 mg/g | a. | 2/74 (2.7) | 1.59 (0.14, 17.48) | 2/61 (3.3) | 1.96 (0.18, 21.66) | 1/56 (1.8) |
| b. | 2/74 (2.7) | 1.59 (0.14, 17.48) | 2/61 (3.3) | 1.96 (0.18, 21.66) | 1/56 (1.8) | |
| Macroalbuminuria UACR >300 mg/g | a. | 6/84 (7.1) | 0.25 (0.10, 0.68)* | 14/84 (16.7) | 0.72 (0.36, 1.43) | 20/90 (22.2) |
| b. | 6/84 (7.1) | 0.26 (0.10, 0.71)* | 13/84 (15.5) | 0.70 (0.34, 1.41) | 19/90 (21.1) | |
aCKD-EPI creatinine; CI=confidence interval; HR=hazard ratio; N=total number, n=number with composite outcome; NA = not applicable; UACR=urinary albumin/creatinine ratio. *p<0.05 versus insulin glargine
Funding
- Commercial Support – Eli Lilly and Company