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.

This article contains supplementary material online at https://doi.org/10.2337/figshare.27997136.

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