Effects of Tirzepatide Versus Insulin Glargine on Cystatin C-Based Kidney Function: A SURPASS-4 Post Hoc Analysis

Diabetes Care. 2023 Aug 1;46(8):1501-1506. doi: 10.2337/dc23-0261.


Objective: Tirzepatide reduces HbA1c and body weight, and creatinine-based estimated glomerular filtration rate (eGFR) decline. Unlike creatine-derived eGFR (eGFR-creatinine), cystatin C-derived eGFR (eGFR-cystatin C) is unaffected by muscle mass changes. We assessed effects of tirzepatide on eGFR-creatinine and eGFR-cystatin C.

Research design and methods: Our primary outcome was eGFR change from baseline at 52 weeks with pooled tirzepatide (5, 10, and 15 mg) and titrated insulin glargine in adults with type 2 diabetes and high cardiovascular risk (SURPASS-4).

Results: Least squares mean (SE) eGFR-creatinine (mL/min/1.73 m2) changes from baseline with tirzepatide and insulin glargine were -2.5 (0.38) and -3.9 (0.38) (between-group difference, 1.4 [95% CI 0.3-2.4]) and -3.5 (0.37) and -5.3 (0.37) (between-group difference, 1.8 [95% CI 0.8-2.8]) for eGFR-cystatin C. Baseline, 1-year, and 1-year change from baseline values significantly correlated between eGFR-cystatin C and eGFR-creatinine. Measures of eGFR changes did not correlate with body weight changes.

Conclusions: Tirzepatide slows the eGFR decline rate, supporting a kidney-protective effect.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Weight
  • Creatinine
  • Cystatin C / pharmacology
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glomerular Filtration Rate / physiology
  • Humans
  • Insulin Glargine / therapeutic use
  • Kidney


  • Insulin Glargine
  • tirzepatide
  • Cystatin C
  • Creatinine

Associated data

  • figshare/10.2337/figshare.22817039