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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

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • L Heerspink, Hiddo Jan, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands
  • Sattar, Naveed, University of Glasgow, Glasgow, Glasgow, United Kingdom
  • Pavo, Imre, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Haupt, Axel, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Yang, Zhengyu, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Wiese, Russell J., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Hemmingway, Andrea, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Cherney, David, Toronto General Hospital, Toronto, Ontario, Canada
  • Tuttle, Katherine R., Providence Washington, Seattle, Washington, United States
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 (eGFRcreatinine) decline vs. insulin glargine (iGLAR). As weight reduction affects muscle mass, eGFRcreatinine may change independently of kidney function, while cystatin C-based eGFR (eGFRcystatin C) is not similarly affected. The aim of this analysis was to determine whether the effect of TZP on kidney function was confirmed by eGFRcystatin 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 eGFRcystatin C was significantly less with TZP vs. iGLAR (Table). No statistically significant interaction was observed in subgroup analyses by baseline UACR, eGFRcreatinine, 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. eGFRcystatin 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 eGFRcystatin C (r=0.054, p=0.125) or eGFRcreatinine (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