3093-LB: Metabolic Response to Oral Semaglutide in Adults with Obesity—Weight Loss and Beyond: The GAROS Prospective Study

Introduction and Objective: Oral semaglutide is effective for weight reduction in obesity, but most data focus on weight loss alone. Prospective evidence on broader metabolic outcomes - body composition, glycemic remission, and what happens after treatment cessation - remains limited. Methods: In the GAROS (Genetics of the Acute Response to Oral Semaglutide) prospective study, 1,100 adults aged 18-65 with BMI ≥25 kg/m² and normoglycemia or prediabetes received oral semaglutide escalated to 42 mg/day over 8 weeks and maintained for 4 weeks. DXA body composition and OGTT were performed at baseline and 12 weeks. Prediabetes remission was defined as reversion to normoglycemia (fasting glucose 100, 2h glucose 140 mg/dL, HbA1c 5.7%). Weight was followed for 6 months after treatment discontinuation. Results: Among participants completing 12-week treatment (median age 43 IQR 35-51; 63% female; median BMI 35.1; 58% prediabetes), mean weight loss was −8.6±4.1% (−8.9 kg; p0.001), with 81.7% achieving ≥5% and 34.1% ≥10% weight loss. By DXA, fat mass decreased by 5.6 kg and lean mass by 3.3 kg; 63% of total weight lost was fat mass, consistent across responder categories (61-64%). Among patients with OGTT-confirmed prediabetes, 70% achieved normoglycemia at 12 weeks. GI adverse events occurred in 76% (nausea 64%); nausea was associated with greater weight loss (p0.001). After treatment cessation, participants remained 7.1% below baseline weight at 3 months and 5.4% at 6 months, with 74% individuals still below starting weight at 6 months. Greater on-treatment weight loss predicted maintenance of body mass (p0.001). Conclusion: Oral semaglutide produced substantial weight loss with favorable body composition, high rates of OGTT-confirmed prediabetes remission, and durable weight benefit persisting 6 months after discontinuation, with durability proportional to initial response. These data characterize the metabolic response to oral semaglutide beyond weight reduction alone. Disclosure L. Szczerbinski: Research Support; Current; Novo Nordisk. Consultant; Current; Eli Lilly and Company. P. Konopka: None. A. Janucik: None. A. Citko-Rojewska: None. A. Paszko: None. A. Golonko: None. J. Mercader: None. M. Udler: Advisory Panel; Ended; Novo Nordisk. Research Support; Current; Novo Nordisk. J.C. Florez: Research Support; Current; Novo Nordisk. Consultant; Current; Alveus Therapeutics. A. Kretowski: None. Funding Supported by funds from the Ministry of Education and Science of Poland within the project Excellence Initiative - Research University, the Ministry of Health of Poland within the project Center of Artificial Intelligence in Medicine at the Medical University of Bialystok, and the Medical Research Agency within the project Regional Center for Digital Medicine at the Medical University of Bialystok (grant number 2023/ABM/02/00008).