754-P: Effect of Retatrutide on Kidney Parameters in People with Type 2 Diabetes and/or Obesity—A Post-Hoc Analysis of Two Phase 2 Trials

The prevalence of chronic kidney disease due to T2D and obesity is rapidly increasing. Retatrutide (RETA), an agonist of GIP, GLP-1 and glucagon receptors, showed marked effects in reducing body weight and HbA1c in people with T2D and/or obesity/overweight (OB). This post-hoc analysis assessed the impact of RETA on kidney parameters. Data from all participants in 2 phase 2 studies were included: T2D (N=281): RETA (0.5, 4, 8, 12 mg) vs dulaglutide 1.5 mg vs PBO (N=45-50/arm); OB (non-T2D; N=338): RETA (1, 4, 8, 12 mg) vs PBO (N=62-70/arm). Assessments included CKD-EPI creatinine eGFR (Cr-eGFR), cystatin C-based eGFR and urine albumin-to-creatinine ratio (UACR). Change from baseline was analyzed using mixed models for repeated measures; pairwise contrasts were used to compare RETA to PBO. At 36 wks in T2D, no difference was observed in Cr-eGFR between all RETA groups and PBO; UACR was significantly reduced vs PBO with RETA 12 mg (Fig). In OB, RETA 8 and 12 mg increased Cr-eGFR and decreased UACR compared to PBO at 48 wks. Results were similar when GFR was estimated from cystatin C. Blood pressure (BP) was significantly reduced in both studies. RETA 8 and 12 mg increased eGFR in people with OB but not in those with T2D. UACR and BP were reduced vs PBO with higher doses of RETA in both trials. These data suggest possible benefits on kidney function that warrant further investigation in larger populations. 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. Z. Lu: None. Y. Du: None. K.L. Duffin: Employee; Eli Lilly and Company. T. Coskun: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. A. Haupt: Employee; Lilly Diabetes. Stock/Shareholder; Lilly Diabetes. M.L. Hartman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company