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

Jan 2, 2025Diabetes care

Tirzepatide linked to lower protein in urine in people with type 2 diabetes: combined analysis of clinical trials

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Abstract

Tirzepatide reduced urine albumin-to-creatinine ratio (UACR) by an adjusted mean of -26.3% compared to pooled comparators at week 40/42.

The percentage change in UACR for tirzepatide was -19.3% for 5 mg, -22.0% for 10 mg, and -26.3% for 15 mg.
Similar reductions in UACR were observed across pooled placebo, active, and insulin comparator studies.
Greater UACR reductions were noted in subgroups with baseline UACR ≥30 mg/g.
Mediation analysis indicated that about half of the UACR reduction may be related to weight loss.
There was no significant difference in estimated glomerular filtration rate (eGFR) between tirzepatide and comparators at week 40/42.

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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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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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