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

Objective: Tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, reduced urine albumin-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 (95% CI) mean percent change from baseline in UACR for tirzepatide 5, 10, or 15 mg compared with all pooled comparators was -19.3% (-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 suggested that approximately 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 clinically relevant decreased UACR versus comparators, suggesting a potential kidney-protective effect.