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

Abstract

OBJECTIVE Tirzepatide, a long-acting, glucose-dependent insulinotropic polypeptide/glucagonlike 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 adjustedmean percent change frombaseline in UACR for tirzepatide 5, 10, or 15mg compared with all pooled comparators was 219.3% (95% CI 225.5, 212.5), 222.0% (228.1, 215.3), and 226.3 (232.0, 220.0), 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.