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Cited by 53Diabetes Treatment and ManagementChronic Kidney Disease and DiabetesDiabetes Management and Research

Tirzepatide Associated With Reduced Albuminuria in Participants With Type 2 Diabetes: Pooled Post Hoc Analysis From the Randomized Active- and Placebo-Controlled SURPASS-1–5 Clinical Trials

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Apperloo, Ellen M., Tuttle, Katherine R., Pavo, Imre, Haupt, Axel, Taylor, Rebecca, Wiese, Russell J., Hemmingway, Andrea, Cherney, David Z.I. +2 more·2025·Diabetes Care
DOI 10.2337/dc24-1773PMC PMC11870291
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Abstract

OBJECTIVE: Tirzepatide, a long-acting, glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, reduced urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline in people with type 2 diabetes and high cardiovascular risk in the SURPASS-4 trial. To examine the generalizability of these findings, we assessed change from baseline in UACR for tirzepatide (5, 10, and 15 mg) compared with active and placebo treatment in a broad population from the SURPASS-1–5 trials. RESEARCH DESIGN AND METHODS: This post hoc analysis examined data from the overall pooled SURPASS-1–5 population and subgroups defined by baseline UACR ≥30 mg/g. A mixed model for repeated measures was used to analyze on-treatment data from baseline to the end-of-treatment visit. Study identifier was included in the model as a covariate. RESULTS: The adjusted mean percent change from baseline in UACR for tirzepatide 5, 10, or 15 mg compared with all pooled comparators was −19.3% (95% CI −25.5, −12.5), −22.0% (−28.1, −15.3), and −26.3 (−32.0, −20.0), respectively, at week 40/42. Results were similar across pooled placebo, active, and insulin comparator studies. UACR lowering appeared more pronounced in subgroups with UACR ≥30 mg/g. Mediation analysis findings suggested that approximately one-half of the reduction in albuminuria associated with tirzepatide may be weight loss related. There was no difference in eGFR between tirzepatide and pooled comparators at week 40/42. CONCLUSIONS: In this post hoc analysis in people with type 2 diabetes, including those with chronic kidney disease, tirzepatide was associated with a clinically relevant decreased UACR versus comparators, suggesting a potential kidney-protective effect.

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  • Preliminary data from the SURPASS program indicate that tirzepatide slowed eGFR decline in comparison with both placebo and comparator drugs including insulin glargine.

    “Preliminary data point toward beneficial effects of GIP agonism, as reported in findings from the SURPASS program that tirzepatide reduced UACR and slowed down eGFR declined in comparison with both placebo (53) and comparator drugs including insulin glargine (74, 75).”

    From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [53]

    The Introduction (page unavailable) reports that a SURPASS-4 post hoc analysis associated tirzepatide with slower eGFR decline than insulin glargine. But this paper’s Conclusions (page unavailable) state that its pooled SURPASS-1–5 analysis found no effect on eGFR over time compared with active or placebo comparators. The insulin-glargine finding is supported; the broader claim of slower eGFR decline across comparators is not. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Preliminary data from the SURPASS program indicate that tirzepatide reduced UACR in comparison with both placebo and comparator drugs including insulin glargine.

    “Preliminary data point toward beneficial effects of GIP agonism, as reported in findings from the SURPASS program that tirzepatide reduced UACR and slowed down eGFR declined in comparison with both placebo (53) and comparator drugs including insulin glargine (74, 75).”

    From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [53]

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Research works printed but not linked: 15

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Authors
Apperloo, E. M., Tuttle, K. R., Pavo, I., Haupt, A., Taylor, R., Wiese, R. J., Hemmingway, A., Cherney, D. Z. I., Sattar, N., & Heerspink, H. J. L.
Affiliations
  • University Medical Center Groningen (NL)
  • University of Washington (US)
  • Eli Lilly (United States) (US)
  • University of Toronto (CA)
  • University of Glasgow (GB)
Corresponding author
Heerspink, Hiddo J.L.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2025-01-02
Volume
48
Issue
3
Pages
430-436
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc24-1773
PMC
PMC11870291
OpenAlex
W4406010846
Cited by
53
References
9
Citations by year
2026: 26 · 2025: 27
FWCI
36.15
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/journals/pages/license (vor)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
Eli Lilly and Company
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
tirzepatide, albuminuria, type 2 diabetes, GLP-1 receptor agonists, albumin-creatinine ratio, estimated glomerular filtration rate, chronic kidney disease, renal protection, weight loss, SURPASS trials, mediation analysis
MeSH terms
Tirzepatide, Aged, Albuminuria, Diabetes Mellitus, Type 2, Female, Glomerular Filtration Rate, Humans, Hypoglycemic Agents, Male, Middle Aged

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