1966-LB: Efficacy and Safety of Semaglutide 7.2 mg in Obesity—STEP UP Trial

Introduction and Objective: To assess efficacy and safety of semaglutide (sema) 7.2 mg in adults with obesity. Methods: This multicenter, double-blind trial (NCT05646706) included adults with BMI ≥30 kg/m2 without T2D, randomized 5:1:1 to once-weekly s.c. sema 7.2 mg, 2.4 mg or placebo (pbo) plus lifestyle intervention, for 72 weeks with 9-week off-treatment follow-up. Co-primary endpoints were relative weight loss (%WL) and proportion reaching ≥5% WL with sema 7.2 mg vs pbo from baseline to week 72. Confirmatory endpoints were %WL with 7.2 mg vs 2.4 mg, waist circumference (WC) change (cm) and proportion reaching ≥10% to ≥25% weight loss thresholds vs pbo and ≥20% and ≥25% vs 2.4 mg. Safety was assessed. Results: In total (7.2 mg, n=1005; 2.4 mg, n=201; pbo, n=201), 74% were female, mean age was 47 yrs, weight 113 kg, BMI 39.9 kg/m2 and WC 119 cm. Most treatment completers reached the max dose (7.2 mg, 75.4%; 2.4 mg, 89.3%; pbo, 96.5%). Mean %WL was greater with sema 7.2 mg (18.7%) vs 2.4 mg (15.6%) or pbo (3.9%) (p<0.001), with significant differences in attainment of %WL thresholds (Fig.). WC was reduced with sema 7.2 mg vs pbo (p<0.001). Gastrointestinal adverse events (AEs) reported by 70.8%, 61.2% and 42.8% of participants with sema 7.2 mg, 2.4 mg and pbo, respectively; 3.3%, 2.0% and 0% discontinued due to these AEs. Serious AEs reported by 6.8%, 10.9% and 5.5% of participants, respectively. Conclusion: Sema 7.2 mg was superior to 2.4 mg and pbo for %WL in adults with obesity, with a similar safety profile to sema 2.4 mg. Disclosure S. Wharton: Advisory Panel; Novo Nordisk A/S, Eli Lilly and Company, Boehringer-Ingelheim, AstraZeneca, Amgen Inc, Biohaven. 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. J. Hjelmesæth: Other Relationship; Novo Nordisk, Eli Lilly and Company. Advisory Panel; IQVIA Inc. M. Kabisch: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. K. Kandler: Employee; Novo Nordisk A/S. 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. M. de Los Angeles Quiroga: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company, Genmab. 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. 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.