Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes
Open accessAbstract
Key Points: People with obesity and/or type 2 diabetes are at higher risk of progressive kidney function loss. We assessed the association of tirzepatide use with kidney function parameters in people with overweight/obesity with or without type 2 diabetes. Tirzepatide treatment was associated with urine albumin-to-creatinine reduction after 24 weeks, which was sustained through week 72, and no change in eGFR. Background: Tirzepatide, a once-weekly, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, showed kidney-protective effects in people with type 2 diabetes at high cardiovascular disease risk. In this post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials, we assessed the association of tirzepatide use with kidney function parameters in people with overweight/obesity with or without type 2 diabetes. Methods: In SURMOUNT-1, participants with overweight or obesity without type 2 diabetes were randomized to tirzepatide 5, 10, and 15 mg or placebo. In SURMOUNT-2, participants with type 2 diabetes were randomized to tirzepatide 10 and 15 mg or placebo. For this analysis, all tirzepatide groups were pooled in each trial. Assessments included change from baseline to week 72 for urine albumin-to-creatinine ratio (UACR) and eGFR. eGFR was assessed using creatinine-based eGFR, cystatin-C–based eGFR, and creatinine-cystatin-C–based eGFR (Cr-Cys-C-eGFR). Results: In SURMOUNT-1 ( N =2539) and SURMOUNT-2 ( N =938), the median (25th–75th percentile) baseline UACR was 6.0 (4.0–11.0) mg/g and 13.0 (6.0–35.1) mg/g, respectively. UACR estimated difference for tirzepatide versus placebo, at week 72 was−8.4% (95% confidence interval [CI], −14.7 to −1.6) for SURMOUNT-1 and −31.1% (95% CI, −40.9 to −19.7) for SURMOUNT-2. The UACR change was more pronounced among participants with baseline UACR ≥30 mg/g with placebo-corrected changes from baseline at week 72 of −42.3% (95% CI, −60.8 to −15.0) in SURMOUNT-1 and −55.2% (95% CI, −68.5 to −36.4) in SURMOUNT-2, respectively. In SURMOUNT-1, tirzepatide was associated with increased eGFR based on cystatin-C–based eGFR or Cr-Cys-C-eGFR estimation equations, with mean differences versus placebo at week 72 of 3.2 ml/min per 1.73 m 2 (95% CI, 2.1 to 4.3) and 1.9 ml/min per 1.73 m 2 (95% CI, 0.9 to 2.9), respectively. In SURMOUNT-2 at week 72, increases in both tirzepatide and placebo groups were observed for Cys-C or Cr-Cys-C-eGFR, with no between-group differences. Conclusions: In participants with obesity/overweight with or without type 2 diabetes, tirzepatide was associated with reduced albuminuria without adverse changes in eGFR. Clinical Trial registry name and registration number: SURMOUNT-1: NCT04184622; SURMOUNT-2: NCT04657003.
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Tirzepatide shows favorable shifts in renal biomarkers in people with obesity and no diabetes.
“SURMOUNT-1 post hoc analyses confirmed favorable shifts in renal biomarkers in participants with obesity and no diabetes [19].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [19]
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- Authors
- Heerspink, H. J. L., Friedman, A. N., Bjornstad, P., van Raalte, D. H., Cherney, D., Cao, D., Garcia-Pérez, L.-E., Stefanski, A., Turfanda, I., Bunck, M. C., Benabbad, I., Griffin, R., & Piras de Oliveira, C.
- Affiliations
- University Medical Center Groningen (NL)
- Indiana University School of Medicine (US)
- University of Washington (US)
- Amsterdam University Medical Center, Amsterdam, The Netherlands
- University Health Network (CA)
- Eli Lilly (United States) (US)
- Eli Lilly and Company, Indianapolis, Indiana
- Corresponding author
- Heerspink, Hiddo J.L.
- ORCID
- Venue
- Journal of the American Society of Nephrology
- Published
- 2025-06-13
- Volume
- 36
- Issue
- 11
- Pages
- 2190-2200
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- PMC
- PMC12591676
- OpenAlex
- W4411276022
- Cited by
- 20
- References
- 32
- Citations by year
- 2026: 11 · 2025: 9
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of the American Society of Nephrology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company, manufacturer of tirzepatide
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- tirzepatide, obesity, type 2 diabetes, renal function, albuminuria, albumin-creatinine ratio, estimated glomerular filtration rate, cystatin C, renal safety, GIP/GLP-1 receptor agonist, weight loss, cardiovascular risk, kidney disease progression
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