Kidney Week

Abstract: FR-OR47

Effect of Tirzepatide on Kidney Function in People with Excess Body Weight: A Post Hoc Analysis of the SURMOUNT-1 Trial

Session Information

• Interventions to Reduce CKD Progression
  November 03, 2023 | Location: Room 119, Pennsylvania Convention Center
  Abstract Time: 05:24 PM - 05:33 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

• Friedman, Allon N., Indiana University School of Medicine, Indianapolis, Indiana, United States

Allon N. Friedman,

• Bjornstad, Petter, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States

Petter Bjornstad,

• van Raalte, Daniël H., Amsterdam Universitair Medische Centra, Duivendrecht, Noord-Holland, Netherlands

Daniël H. van Raalte,

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

Zhengyu Yang,

• Stefanski, Adam, Eli Lilly and Company, Indianapolis, Indiana, United States

Adam Stefanski,

• Chigutsa, Farai B., Eli Lilly and Company, Indianapolis, Indiana, United States

Farai B. Chigutsa,

• Turfanda, Ibrahim, Eli Lilly and Company, Indianapolis, Indiana, United States

Ibrahim Turfanda,

• Bunck, Mathijs, Eli Lilly and Company, Indianapolis, Indiana, United States

Mathijs Bunck,

• Piras de Oliveira, Carolina, Eli Lilly and Company, Indianapolis, Indiana, United States

Carolina Piras de Oliveira,

Background

The prevalence of chronic kidney disease due to obesity is rapidly increasing, but few proven effective therapies are available. Tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown potential in attenuating the decline in estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D) at high risk for cardiovascular disease. In the SURMOUNT-1 trial in people with obesity or overweight without T2D, tirzepatide significantly reduced body weight and blood pressure by week 72 (the primary endpoint) compared with placebo. This post-hoc analysis assessed the potential impact of tirzepatide compared with placebo on kidney function in SURMOUNT-1 trial participants.

Methods

Data from all participants randomly assigned to treatment were included (pooled tirzepatide [5, 10, and 15 mg], N = 1896; placebo, N = 643). Assessments included CKD-EPI creatinine- and cystatin-C-based eGFR (Cr-eGFR and CysC-eGFR, respectively), and urine albumin-to-creatinine ratio (UACR). The change from baseline to week 72 was analyzed using a mixed model for repeated measures with on-treatment data.

Results

Baseline mean Cr-eGFR was 98.1±18.0 mL/min/1.73m² and CysC-eGFR was 95.5±19.1 mL/min/1.73m²; 27%-36% of participants had mean eGFR <90 mL/min/1.73m². Baseline median UACR was 6.0 mg/g (interquartile range 4.0-11.0 mg/g); 8.6% of participants had UACR ≥30 mg/g. The estimated treatment difference (ETD) between pooled tirzepatide groups and placebo on the change from baseline Cr-eGFR was -0.2 mL/min/1.73m² (95% confidence interval [CI] -1.2, 0.9; p=0.780). For CysC-eGFR the ETD was 3.2 mL/min/1.73m² (95% CI 2.1, 4.3; p<0.001). The ETD on the percent change in UACR was -8.4% (95% CI -14.7, -1.6; p=0.017). In participants with baseline UACR ≥30 mg/g, the ETD was -42.3% (95% CI -60.8, -15.0; p=0.006).

Conclusion

Tirzepatide demonstrated an increase in CysC-eGFR and reductions in UACR compared with placebo, suggesting renoprotective effects. These results warrant a long-term, prospective kidney outcome trial for people with obesity or overweight.

Funding

• Commercial Support – Eli Lilly and Company