Kidney Week

Abstract: TH-PO1241

TREASURE-CKD: Tirzepatide Mechanism of Action Study on Kidney Structure and Function

Session Information

• Late-Breaking Research Posters
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• van Raalte, Daniël H., Amsterdam Universitair Medische Centra, Amsterdam, NH, Netherlands

Daniël H. van Raalte, MD, PhD

• Cherney, David, University Health Network, Toronto, Ontario, Canada

David Cherney, MD, PhD

• Koeneman, Lisette, Eli Lilly and Company, Indianapolis, Indiana, United States

Lisette Koeneman, MD

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

Fady T. Botros, PhD

• Blondin, Denis P., Universite de Sherbrooke, Sherbrooke, Quebec, Canada

Denis P. Blondin, PhD

• Hurt, Karla C, Eli Lilly and Company, Indianapolis, Indiana, United States

Karla C Hurt, RN

• Wu, Peikun, Eli Lilly and Company, Indianapolis, Indiana, United States

Peikun Wu, MS

• Kurani, Ajay, Eli Lilly and Company, Indianapolis, Indiana, United States

Ajay Kurani, MS, PhD

• Bjornstad, Petter, University of Washington School of Medicine, Seattle, Washington, United States

Petter Bjornstad, MD

Background

Tirzepatide (TZP), a dual GIP and GLP-1 receptor agonist, is associated with improved cardiac and kidney outcomes. The TREASURE-CKD trial explored TZP's kidney mechanisms of action in participants with obesity or overweight and chronic kidney disease (CKD), with or without type 2 diabetes (T2D) over 52 weeks (W52) of treatment.

Methods

Participants with CKD (eGFR ≥25-≤60 or eGFR ≥25-≤75 mL/min/1.73 m² if UACR >30 mg/g) were randomized 1:1 to once-weekly TZP maximum tolerated dose up to 15 mg or matched placebo (PBO). The primary endpoint was percent change from baseline to W52 in renal sinus fat (kidney MRI) for TZP vs. PBO. Secondary endpoints included body weight, eGFR, UACR, and MRI-based kidney fat content. Exploratory endpoints included HbA1c, lipid profiles, and hsCRP. In a subset of participants (n=36), [¹¹C]acetate kidney PET/CT assessed kidney oxidative metabolism (k₂) and perfusion-oxidative metabolism coupling (k₂/F).

Results

Of 134 participants randomized (TZP: n=66; PBO: n=68), mean age was 62 (SD 13) years, 46% were female, 77% were White, 42% had T2D, and 43% were on SGLT-2 inhibitors at baseline. Mean BMI was 36.0 (7.9) kg/m², eGFR_creat 49.6 (10.5) mL/min/1.73 m²; median UACR 36.0 (IQR: 11.8-172.0) mg/g. Renal sinus fat did not change significantly with TZP vs. PBO, whereas kidney parenchyma fat content significantly decreased with TZP vs. PBO (-17.6%; p<0.001). TZP was associated with a significant decrease in renal retroperitoneal fat (-26.4%; p<0.001) vs. PBO. TZP vs. PBO reduced body weight (-16.4%), was associated with reductions in HbA1c
(-1.35% in T2D and -0.52% in non-T2D), hsCRP (-60.7%), and triglycerides (-30.3%), and with increases in HDL-C (13.2%) (all p<0.001). eGFR_creat increased at W52 by 3.7 mL/min/1.73 m² (p<0.05), while UACR was lowered by 46.6% vs. baseline for TZP. In participants with PET data, TZP was associated with reduced medullary k₂/F vs. PBO (-20.1%; p<0.05).

Conclusion

In participants with obesity or overweight and CKD with or without T2D, TZP was associated with reduced kidney fat compartments and clinically relevant improvements in body weight, HbA1c, hsCRP, UACR, and lipids. TZP was also associated with improved medullary perfusion-metabolism coupling, suggestive of increased kidney metabolic efficiency, helping substantiate the mechanistic basis for the potential kidney-protective effects of TZP.

Funding

• Commercial Support – Eli Lilly and Company