In SURPASS 4, the GIP/GLP-1 receptor agonist tirzepatide (TZP) showed a potential kidney protective effect in people with T2D and high CV risk by slowing the rate of eGFR decline and reducing urine albumin-creatinine ratio (UACR) vs insulin glargine over 2 years. In this post-hoc analysis, we explored effects of TZP on UACR changes in SURPASS 1-5 trials. UACR (% difference) for TZP (5, 10, 15 mg) 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 1 mg] & 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. 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.


H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck & Co., Inc., Janssen Research & Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals. I.Pavo: Employee; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. Z.Yang: Employee; Eli Lilly and Company. R.Wiese: Employee; Eli Lilly and Company. A.Hemmingway: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. N.Sattar: Advisory Panel; Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Novartis, Roche Diagnostics, Consultant; Afimmune Limited, Hanmi Pharm. Co., Ltd., Pfizer Inc., Other Relationship; Abbott, AstraZeneca, Boehringer Ingelheim Pharma GmbH&Co.KG, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim Pharma GmbH&Co.KG, Novartis, Roche Diagnostics.


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