1733-P: Effect of Mazdutide on Kidney Function in Adults with Obesity or Overweight

Introduction and Objective: Mazdutide (MAZ; LY3305677), a dual agonist of the GLP-1 and glucagon receptors, was previously shown to reduce body weight (up to 22.3% at 48 weeks) vs placebo (PBO), with mild-to-moderate gastrointestinal events as the most common TEAEs. We examined whether MAZ also improved measures of kidney function. Methods: In this Phase 2 study (NCT06124807), adults (N=179) with BMI ≥30 kg/m², or BMI ≥27 kg/m² with weight-related comorbidities, excluding T2D, were randomly assigned to 48 weeks of once-weekly subcutaneous MAZ 3/6 mg (dose escalation at W32; n=32), 10 mg (n=48), 16 mg (n=51), or PBO (n=48). Changes from baseline (CFB) in selected kidney parameters were estimated using a mixed model for repeated measures (MMRM), presented as least squares means and standard errors (SE). Results: At W32, cystatin C-derived eGFR increased significantly from baseline vs PBO with MAZ 10 mg (CFB [SE] in mL/min/1.73 m²: 7.7 [1.6]; p <0.001) and MAZ 16 mg (7.2 [2.1]; p=0.006), compared with -0.3 [1.6] for PBO. Urine albumin-to-creatinine ratio (UACR) decreased significantly from baseline vs PBO in all MAZ groups: -39.8% [10.8] for 3/6 mg (p=0.028), -36.2% [6.1] for 10 mg (p=0.007), -32.7% [7.7] for 16 mg (p=0.030), compared with -4.2% [11.1] for PBO at W32. The higher doses also achieved clinically relevant decreases in systolic blood pressure at W32 and W48. Conclusion: Compared to placebo, MAZ improved eGFR and UACR, suggesting benefits in kidney function in adults with obesity/overweight without T2D. Disclosure S. Hsia: Research Support; Current; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH. Research Support; Ended; Biomea Fusion, Inc. Research Support; Current; Corcept Therapeutics, Currax Pharmaceuticals. Research Support; Ended; Inventiva Pharma. Research Support; Current; Eli Lilly and Company, Novo Nordisk A/S, Regor Pharmaceuticals, Inc., Sparrow Pharmaceuticals, Viking Therapeutics, Zealand Pharma A/S. H.E. Bays: Research Support; Current; 89bio, Inc., Alon Medtech/Epitomee, Altimmune, Amgen Inc., AstraZeneca, Bioage, Boehringer Ingelheim International GmbH, Carmot Therapeutics, Inc., Eli Lilly and Company, Graviton, Merck & Co., Inc., Metsera, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Regeneron Pharmaceuticals Inc., Birdrock, Tern, Viking Therapeutics, Vivus, Zomagen. Advisory Panel; Current; 89bio, Inc., Altimmune, Amgen Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Regeneron Pharmaceuticals Inc., Rivus, Zomagen, zyversa. Research Support; Current; Kailera. Advisory Panel; Current; Merck & Co., Inc. L.K. Billings: Advisory Panel; Current; Novo Nordisk, Lilly, Sanofi, Amgen Inc., Bayer AG. A.K. Weideman: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. O. Ferreira Galvao de Araujo: Employee; Current; Eli Lilly and Company. S. Gurbuz: Employee; Current; Eli Lilly and Company. T. Coskun: Employee; Current; Eli Lilly and Company. A. Haupt: Employee; Ended; Lilly. Stock/Shareholder; Ended; Lilly. M. Thomas: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. K.J. Mather: Employee; Current; Eli Lilly and Company.