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Tirzepatide (TZP), a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown kidney protective effects in people with type 2 diabetes (T2D) at high risk for cardiovascular disease. In the SURMOUNT-2 (SM-2) trial in people with obesity or overweight with T2D, at 72 weeks TZP significantly reduced body weight by up to 15.7%, HbA1c by 2.22%, and systolic and diastolic blood pressure by 7.7mmHg and 2.9mmHg respectively. This post-hoc analysis assessed the potential impact of TZP vs PBO on kidney parameters in SM-2 trial participants. Data from all participants randomly assigned to treatment were included (pooled TZP 10 and 15 mg, N = 623; PBO, N = 315). Assessments included CKD-EPI creatinine-cystatin-C-based eGFR (Cr-Cys-C-eGFR), and urine albumin-to-creatinine ratio (UACR). The change from baseline to week 72 was analyzed using mixed models for repeated measures with on-treatment data. Baseline mean Cr-Cys-C-eGFR was 91.3±19.5 mL/min/1.73m2. The estimated treatment difference (ETD) between pooled TZP groups and PBO on the change from baseline in Cr-Cys-C-eGFR was 0.0 mL/min/1.73m2 (95% confidence interval CI -1.7, 1.7; p=0.993). TZP compared to placebo did not change Cr-Cys-C-eGFR at week 72 in participants with baseline Cr-Cys-C-eGFR 60 ml/min/1.73m2 (p=0.180) or ≥ 60 ml/min/1.73m2 (p=0.714). Baseline median UACR was 13.0 mg/g (interquartile range 6.0-35.0 mg/g). UACR significantly decreased with TZP vs. PBO (ETD -31.1 %, 95% CI -40.9, -19.7, p0.001) and for those with baseline UACR ≥30 mg/g, the ETD was -55.2% (95% CI -68.5, -36.4; p0.001). In this SM-2 trial population of participants with obesity or overweight with T2D and preserved eGFR at baseline, TZP reduced albuminuria without adversely affecting eGFR. Disclosure H.L. Heerspink: Consultant; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, CSL Behring, Eli Lilly and Company. Advisory Panel; Gilead Sciences, Inc. Consultant; Janssen Pharmaceuticals, Inc., Novartis AG, Novo Nordisk, Traveere Pharmaceuticals. A. Friedman: Advisory Panel; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Advisory Panel; GI Dynamics, Gila Therapeutics, AstraZeneca. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. D. van Raalte: Consultant; Eli Lilly and Company. Research Support; Eli Lilly and Company, Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; Merck Merck Bayer Inc. D. Cao: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. L. Garcia-Perez: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Stefanski: Employee; Eli Lilly and Company. I. Turfanda: Employee; Eli Lilly and Company. M.C. Bunck: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. I. Benabbad: Employee; Eli Lilly and Company. C. Piras de Oliveira: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. R. Griffin: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company
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