(DCP064) TIRZEPATIDE REDUCES ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES: POST-HOC POOLED ANALYSIS OF SURPASS 1-5

Background: A post-hoc analysis of the SURPASS 4 trial suggested that the glucose-dependent insulinotropic polypeptide/ glucagon-like peptide-1 (GIP/GLP-1) receptor agonist tirzepatide (TZP) could have a potential kidney protective effect in people with T2D and high cardiovascular risk by slowing the rate of estimated glomerular filtration rate (eGFR) decline and reducing urine albumin-creatinine ratio (UACR) vs insulin glargine over 2 years. In the current post-hoc analysis, we explored effects of TZP on UACR changes in SURPASS 1-5 trials.

METHODS AND RESULTS: UACR (% difference) for TZP (5, 10, 15mg) vs comparators (COMPs) was analyzed. Analyses were conducted in the pooled entire SURPASS 1-5 population and populations pooled by COMP: placebo (SURPASS 1 & 5); active (SURPASS 2 [semaglutide 1mg] & SURPASS 3-4 [insulins]); and insulins. In each pooled population, data were examined in all patients and in subgroups defined by baseline UACR ≥30 mg/g or eGFR < 60 mL/min/1.73m2. Mixed model for repeated measures was used to analyze on-treatment data from baseline up to the end of treatment visit. UACR data was available in 6263 patients of whom 1846 had UACR ≥30 mg/g and 537 had eGFR < 60 mL/min/1.73m2. UACR decreased more with TZP 5, 10, and 15 mg vs COMPs in pooled SURPASS 1-5 and consistently across pooled placebo, active, and insulin COMP studies (Table). UACR lowering appeared more pronounced in subgroups with baseline UACR ≥30 mg/g or eGFR < 60 mL/min/1.73m2.

Conclusion: In people with T2D, including those with reduced kidney function, TZP decreased UACR vs COMPs to a clinically relevant degree, supporting a potential kidney protective effect.