1971-LB: Impact of Semaglutide on Kidney, Cardiovascular, and Mortality Outcomes by Baseline BMI and Weight Loss in People with T2D and CKD—Data from the FLOW Trial

Introduction and Objective: In FLOW, semaglutide reduced the risk of kidney, cardiovascular (CV), and mortality outcomes in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). We now test how the benefit of semaglutide relates to baseline BMI and change in body weight (BW). Methods: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo (N= 3,533). The primary kidney outcome was a composite of kidney failure, sustained estimated glomerular filtration rate reduction of ≥50%, or kidney or CV death. Key secondary outcomes included major adverse CV events and all-cause death. Subgroup analyses by BMI used a Cox proportional hazards model; mediation analyses by change in BW used a repeated regression approach. Results: Mean baseline BMI and BW were 32.0 kg/m2 and 89.6 kg, respectively. The effect of semaglutide on the primary kidney outcome, major adverse CV events, and all-cause death was consistent across baseline BMI categories (interaction p value range, 0.6217 to 0.9471) (Figure). The estimated percentage mediation (95% CI) of BW loss was -0.5% (-29.8, 37.8) on the primary kidney outcome; -33.4% (-273.1, 82.0) for major adverse CV events; and -25.6% (-150.5, 34.3) for all-cause death. Conclusion: Semaglutide benefits on kidney, CV, and mortality outcomes were independent of baseline BMI, and did not seem to be explained by change in BW. Disclosure J.F.E. Mann: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Novo Nordisk. Board Member; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk. Other Relationship; Sanofi. Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Novartis AG. Other Relationship; UpToDate Inc / KDIGO. K.R. Tuttle: Consultant; Lilly Diabetes, Boehringer-Ingelheim, Novo Nordisk, Pfizer Inc. Other Relationship; AstraZeneca. Consultant; Bayer Pharmaceuticals, Inc, Traveere Pharmaceuticals, ProKidney. R.E. Pratley: Consultant; AbbVie Inc. Stock/Shareholder; Altanine, Inc. Consultant; Amgen Inc, AstraZeneca. Other Relationship; Bayer AG, Bayer Pharmaceuticals, Inc, Biomea Fusion. Consultant; Boehringer-Ingelheim. Other Relationship; Carmot Therapeutics, Inc, Corcept Therapeutics, Dompé, Eli Lilly and Company, Endogenex. Consultant; Endogenex. Other Relationship; Fractyl Health, Inc., Gasherbrum Bio, Inc. Consultant; Genprex, Getz Pharma, Hanmi Pharm. Co., Ltd, Intas Pharmaceuticals Ltd, Lexicon Pharmaceuticals, Inc, Lilly USA LLC. Speaker's Bureau; Lilly USA LLC. Other Relationship; Metavention, Novo Nordisk, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Other Relationship; Pfizer Inc, Poxel SA. Consultant; Regeneron Pharmaceuticals. Other Relationship; Sanofi. Consultant; Scholar Rock. Other Relationship; Sun Pharmaceutical Industries Ltd. K.W. Mahaffey: Research Support; American College of Cardiology, American Heart Association. Consultant; Applied Therapeutics. Research Support; Apple, Inc. Other Relationship; Bayer Pharmaceuticals, Inc. Consultant; Bristol-Myers Squibb Company, BridgeBio. Research Support; California Institute Regenerative Medicine, CSL Behring, Cytokinetics Inc, Eidos, Element. Consultant; Eli Lilly and Company, Elsevier. Research Support; Ferring. Consultant; Fosun Pharma. Research Support; Gilead Sciences, Inc, Google (Verily). Other Relationship; Human. Research Support; Idorsia. Other Relationship; Johnson & Johnson. Research Support; Luitpold. Stock/Shareholder; Medeloop (I have equity in this company). Consultant; Moderna, Inc, Myokardia. Research Support; Myovant. Other Relationship; Novartis. Consultant; Novo Nordisk. Research Support; PAC-12. Consultant; PhaseBio Pharmaceuticals, Inc, Portola. Other Relationship; Precordior. Consultant; Quidel. Stock/Shareholder; Regencor (I have equity in this company). Research Support; Sanifit. Consultant; Scleroderma Foundation. Research Support; St Jude Medical. Consultant; Theravance. M. Arici: Speaker's Bureau; Amgen Inc. Advisory Panel; Astellas Pharma Inc, AstraZeneca. Speaker's Bureau; Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Menarini. Research Support; Novo Nordisk. Speaker's Bureau; Sanofi. Other Relationship; CSL Behring. N. Belmar: Employee; Novo Nordisk A/S. K. Bonefeld: Employee; Novo Nordisk A/S. G. Chernin: None. R. Correa-Rotter: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; Roche Pharmaceuticals. Other Relationship; Boehringer-Ingelheim. Speaker's Bureau; Amgen Inc. Research Support; Lilly USA LLC. Speaker's Bureau; Sanofi. P. Gillard: Research Support; Novo Nordisk A/S, Sanofi, Dexcom, Inc., Tandem Diabetes Care, Inc, Medtronic. Speaker's Bureau; Abbott, Bayer Pharmaceuticals, Inc. Advisory Panel; Ypsomed AG. Speaker's Bureau; Air Liquide. Research Support; Roche Diabetes Care. S. Hadjadj: Consultant; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Speaker's Bureau; Eli Lilly and Company. Research Support; Novartis AG. Consultant; Novo Nordisk. Other Relationship; Sanofi. Advisory Panel; Valbiotis. T. Idorn: Employee; Novo Nordisk A/S. L. Ji: None. M. Linder: Employee; Novo Nordisk A/S. R.E. Schmieder: Research Support; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. M. Shamkhalova: None. A. Sriwijitkamol: None. V. Perkovic: Other Relationship; AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GlaxoSmithKline, HiBio, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, UpToDate. Board Member; St Vincents Health Australia, Mindgardens Neuroscience Network, Kidney Health Australia. Stock/Shareholder; George Clinical. P. Rossing: Speaker's Bureau; Abbott. Advisory Panel; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Gilead Sciences, Inc, Novo Nordisk. Other Relationship; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Daiichi Sankyo.