2700-LB: High-Dose Semaglutide Is Associated with Preservation of Kidney Function in People Living with Obesity without Diabetes

Introduction and Objective: This post hoc analysis of the STEP UP trial investigated changes in kidney function and hsCRP from baseline to week 72 in participants (pts) with obesity without diabetes who received semaglutide (sema) 7.2 mg, sema 2.4 mg, or placebo (pbo). Methods: eGFR was calculated using the CKD-EPI 2021 creatinine (eGFRcre) and creatinine-cystatin C (eGFRcre-cys) equations. Changes in eGFRcre, eGFRcre-cys, eGFR category shifts (60, 60-90, ≥90 mL/min/1.73 m2), and hsCRP at week 72 were assessed. Data are observed values from the on-treatment period. Results: Overall, 1005 pts were randomized to sema 7.2 mg, 201 to sema 2.4 mg, and 201 to pbo. In the sema 7.2 mg, 2.4 mg, and pbo groups, 67.3%, 70.6%, and 69.7% of pts, respectively, had normal kidney function (eGFRcre ≥90 mL/min/1.73m2) at baseline. eGFRcre ratios to baseline at week 72 were similar between groups (Fig A), with few pts changing eGFRcre category. eGFRcre-cys significantly increased with sema 7.2 mg and 2.4 mg vs pbo by week 72 (Fig B), with more pts moving to the eGFRcre-cys ≥90 mL/min/1.73 m2 category. At week 72, pts in both sema groups had significantly greater reductions in hsCRP vs pbo pts (Fig C). Conclusion: When using eGFRcre-cys, which is unaffected by weight loss, sema 7.2 mg and 2.4 mg increased eGFR to a greater degree than placebo. Additionally, sema 7.2 mg and 2.4 mg reduced hsCRP vs pbo, demonstrating reduced systemic inflammation as well as preserved kidney function. Disclosure P. Rossing: Advisory Panel; Ended; Abbott Diagnostics. Advisory Panel; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Eli Lilly and Company. Consultant; Current; Lexicon Pharmaceuticals, Inc., Roche Pharmaceuticals. Consultant; Ended; Amgen Inc. C. Fuchs Jacobsen: Employee; Current; Novo Nordisk A/S. J. Hjelmesæth: Advisory Panel; Current; Novo Nordisk, Lilly. K.J. Kolnes: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. L. Wilson: Employee; Current; Novo Nordisk. K. Tuttle: Consultant; Ended; Alnylam Pharmaceuticals, Inc. Consultant; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Novo Nordisk, Lilly, ProKidney. Consultant; Ended; Roche Diabetes Care. Research Support; Ended; Travere.