1978-LB: Efficacy and Safety of Semaglutide 7.2 mg in Obesity and Type 2 Diabetes—STEP UP T2D Trial

Introduction and Objective: To assess efficacy and safety of semaglutide (sema) 7.2 mg in adults with obesity and T2D. Methods: In a multicenter, double-blind trial (NCT05649137), participants with BMI ≥30 kg/m2 and T2D were randomized 3:1:1 to once-weekly s.c. sema 7.2 mg, 2.4 mg, or placebo (pbo), plus lifestyle intervention for 72 weeks with 9-week follow-up. Co-primary endpoints were weight loss (WL; %) and proportions reaching WL ≥5%; confirmatory endpoints were WL ≥10%, ≥15%, and ≥20%; waist circumference (WC) change (cm); and HbA1c change (%); all for sema 7.2 mg vs pbo (treatment policy estimand). Safety was assessed. Results: Baseline characteristics (N=512) were: female 52%; mean age 56 yrs; body weight 110 kg; BMI 38.6 kg/m2; WC 122 cm; HbA1c 8.1%. Sema 7.2 mg led to greater WL vs pbo (−13.2% vs −3.9%; p<0.001) and vs sema 2.4 mg (−13.2% vs −10.4%; post hoc p=0.003; Fig.). More participants reached WL thresholds with sema 7.2 mg (all p<0.001; Fig.) and had greater reductions in WC (estimated treatment difference [ETD; 95% CI]: −6.5 [−9.0, −4.1]; p<0.001) and HbA1c (ETD [95% CI]: −1.5 [−1.8, −1.2]; p<0.001) vs pbo. Gastrointestinal adverse events (AEs) were reported by 53.1%, 51.5%, and 25.5% of participants with sema 7.2 mg, 2.4 mg, and pbo, and serious AEs by 9.1%, 8.7%, and 8.8%, respectively. Sema 7.2 mg did not increase hypoglycemic episode risk vs 2.4 mg or pbo. Conclusion: Sema 7.2 mg led to greater WL vs comparators, with a safety profile comparable to sema 2.4 mg. Disclosure I. Lingvay: Consultant; Abbvie, Altimmune, Amgen, Alveus Tx, Antag Tx, Astra Zeneca, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Juvena, Keros Ther, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, TERNS Pharma, The Comm Group, WebMD, and Zealand Pharma. Research Support; Novo Nordisk, Sanofi, Boehringer-Ingelheim. S.J. Bergenheim: Employee; Novo Nordisk A/S. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Other Relationship; Mellitus Health. Consultant; Metsera. Other Relationship; Pendulum Therapeutics, Praetego, Stability Health. Consultant; Tandem Diabetes Care, Inc, TERNS Pharmaceuticals, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. P. Freitas: Speaker's Bureau; Eli Lilly and Company, Bayer Pharmaceuticals, Inc, Roche Diagnostics, Novo Nordisk, Merck Sharp & Dohme Corp, Sanofi, Medinfar Portugal, Bial, NKPS Protein Suppleis, Faes Farma. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Eli Lilly and Company, Novo Nordisk, Fractyl Health, Inc., Alnylam Pharmaceuticals, Inc, Zealand Pharma A/S, Allurion, Carmot Therapeutics, Inc, TERNS Pharmaceuticals, Regeneron Pharmaceuticals, Inogen, Neurocrine, Keros Therapeutics. Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens, Roche Pharmaceuticals, Zealand Pharma A/S. N.M. Harder-Lauridsen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. J. Rosenstock: Advisory Panel; Amgen Inc. Research Support; Amgen Inc. Advisory Panel; Applied Therapeutics. Research Support; Applied Therapeutics, AstraZeneca. Advisory Panel; Bayer Pharmaceuticals, Inc, Biomea Fusion, Corcept Therapeutics, Eli Lilly and Company. Research Support; Eli Lilly and Company. Advisory Panel; Hanmi Pharm. Co., Ltd. Research Support; Merck & Co., Inc, Novartis AG. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk, Pfizer Inc. Advisory Panel; Regeneron Pharmaceuticals. Research Support; Regeneron Pharmaceuticals, Regeneron Pharmaceuticals. Advisory Panel; Regor Therapeutics, Roche Pharmaceuticals, Sanofi. Research Support; Sanofi. Advisory Panel; Structure Therapeutics, Inc, Zealand Pharma A/S. K. Sahu: Employee; Novo Nordisk A/S. S. Wharton: Advisory Panel; Novo Nordisk A/S, Eli Lilly and Company, Boehringer-Ingelheim, AstraZeneca, Amgen Inc, Biohaven.