Kidney Week

Abstract: SA-PO269

Effects of Tirzepatide vs. Insulin Glargine on Kidney Function Evaluated by Cystatin C-Based eGFR: A Post Hoc Analysis From the SURPASS-4 Trial

Session Information

• Diabetic Kidney Disease: Clinical - II
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• L Heerspink, Hiddo Jan, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

• Sattar, Naveed, University of Glasgow, Glasgow, Glasgow, United Kingdom

Naveed Sattar,

• Pavo, Imre, Eli Lilly and Company, Indianapolis, Indiana, United States

Imre Pavo,

• Haupt, Axel, Eli Lilly and Company, Indianapolis, Indiana, United States

Axel Haupt,

• Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States

Kevin L. Duffin,

• Yang, Zhengyu, Eli Lilly and Company, Indianapolis, Indiana, United States

Zhengyu Yang,

• Wiese, Russell J., Eli Lilly and Company, Indianapolis, Indiana, United States

Russell J. Wiese,

• Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States

Jonathan Matthew Wilson,

• Hemmingway, Andrea, Eli Lilly and Company, Indianapolis, Indiana, United States

Andrea Hemmingway,

• Cherney, David, Toronto General Hospital, Toronto, Ontario, Canada

David Cherney,

• Tuttle, Katherine R., Providence Washington, Seattle, Washington, United States

Katherine R. Tuttle,

Background

In patients with type 2 diabetes and increased cardiovascular risk (SURPASS-4 trial, N=1995; mean age 64 years, HbA1c 8.5%, BMI 33 kg/m², eGFR [CKD-EPI-creatinine] 81.3 ± 21 mL/min/1.73m²), including 707 (35%) with UACR>30 mg/g and 342 (17%) with eGFR<60 mL/min/1.73m², tirzepatide (TZP) treatment markedly reduced weight and slowed creatinine-based eGFR (eGFR_creatinine) decline vs. insulin glargine (iGLAR). As weight reduction affects muscle mass, eGFR_creatinine may change independently of kidney function, while cystatin C-based eGFR (eGFR_{cystatin C}) is not similarly affected. The aim of this analysis was to determine whether the effect of TZP on kidney function was confirmed by eGFR_{cystatin C}.

Methods

Mixed model for repeated measurements over time was used to analyze on-treatment eGFR data.

Results

After 1-year in the overall study population, the decline from baseline in eGFR_{cystatin C} was significantly less with TZP vs. iGLAR (Table). No statistically significant interaction was observed in subgroup analyses by baseline UACR, eGFR_creatinine, BMI, smoking status, or SGLT2i treatment (Table). Baseline (r=0.765, p<0.0001), 1-year (r=0.771, p<0.0001), and 1-year change from baseline (r=0.326, p<0.0001) values correlated between cystatin- and creatinine-based eGFR. eGFR_{cystatin C} reductions at 1 year were dose dependent (between group difference vs. iGLAR 1.2 [-0.2, 2.7], 2.1 [0.7, 3.6] and 2.0 [0.6, 3.5] mL/min/1.73m² with 5, 10, and 15 mg, respectively). 1-year changes in body weight did not correlate with changes in eGFR_{cystatin C} (r=0.054, p=0.125) or eGFR_creatinine (r=0.012, p=0.728).

Conclusion

The effect of TZP on the slowing of eGFR decline is confirmed by cystatin C-based measurements, supporting the concept of a kidney-protective effect.

Funding

• Commercial Support – Eli Lilly and Company