1134-OR: Reduction in Glomerular Hyperfiltration with Tirzepatide in Youth-Onset T2D

Introduction and Objective: Tirzepatide (TZP) demonstrated improvements in glycemic control and BMI in participants with youth-onset type 2 diabetes (YT2D) in SURPASS-PEDS. TZP impact on glomerular hyperfiltration, an early disease marker affecting 24% of YT2D, was not previously assessed. This analysis examined changes in estimated glomerular filtration rate (eGFR) and hyperfiltration status with TZP treatment. Methods: TZP vs PBO was assessed for 30 weeks in participants 10 to <18 years old with YT2D on metformin and/or basal insulin. Participants received TZP 5 mg (n=32), 10 mg (n=33) or PBO (n=34). eGFR was calculated using Zappitelli creatinine-cystatin C equation; hyperfiltration was defined as eGFR ≥126.8 mL/min/1.73 m². Change in eGFR (MMRM) and shifts in hyperfiltration status (Fisher’s exact test) were assessed. Results: At baseline, mean age was 14.7 years old and 18% of participants exhibited hyperfiltration (mean eGFR 142 vs 104 mL/min/1.73m2 in normofiltration). TZP treatment led to a reduction in eGFR at Week 30, with greater than two-times reduction in participants with baseline hyperfiltration (Table 1). The proportion of participants with hyperfiltration decreased in pooled TZP (18.6% to 5.5%) and increased in PBO (16.1% to 21.9%, p<0.05, TZP vs PBO). Conclusion: In the SURPASS-PEDS trial, treatment with tirzepatide was associated with a mean decrease in eGFR, primarily ascribed to attenuation of glomerular hyperfiltration.Trial registration: ClinicalTrials.gov (NCT05260021). Disclosure P. Bjornstad: Consultant; Current; Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. T.S. Hannon: None. J.M. Maldonado: Employee; Current; Eli Lilly and Company. K. Ranta: Employee; Current; Eli Lilly and Company. K. Pamidipati: None. H. Patel: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company. B. Bergman: Employee; Current; Eli Lilly and Company. Stock/Shareholder; Current; Eli Lilly and Company.