2822-LB: Semaglutide Improves Postprandial Glucose Metabolism after Spinal Cord Injury: A First Mechanistic Study

Introduction and Objective: Glucose dysregulation after spinal cord injury (SCI) is characterized by exaggerated postprandial hyperglycemia despite relatively normal fasting glucose, reflecting impaired insulin action, β-cell dysfunction, and disrupted gut-pancreas signaling due to autonomic injury. The metabolic effects of incretin-based therapy in this population are unknown. We examined the effects of the GLP-1 receptor agonist semaglutide on prandial glucose metabolism in individuals with SCI and type 2 diabetes (T2D). Methods: Five men with T2D and SCI (duration 11±4 years; age 53±3 years; BMI 35±3 kg/m²; HbA1c 7±0.5%) underwent a liquid mixed-meal tolerance test (50 g protein + 50 g glucose) at baseline and after 6 months of semaglutide (2 mg weekly). Plasma glucose, insulin, C-peptide, and glucagon were measured to assess glycemia, insulin sensitivity, insulin clearance, and β-cell function. Results: Semaglutide induced significant weight loss (10±1 kg; 16±3% of baseline BW, p<0.05) and reduced HbA1c (−1±0.4%, p=0.06). Total area under the glucose curve decreased by ~30% (p<0.05). Improvements were accompanied by enhanced fasting and prandial insulin sensitivity (HOMA-IR, OGIS) and increased insulin clearance (p<0.05). β-cell function showed a trend toward improvement, while glucagon responses were unchanged. Treatment was well tolerated with mild gastrointestinal symptoms and stable heart rate and blood pressure. Conclusion: In this first mechanistic evaluation of GLP-1 receptor agonist therapy in patients with SCI and T2D, semaglutide markedly improved postprandial glucose tolerance primarily through enhanced insulin action and clearance. These findings support incretin-based therapy as a promising strategy to address metabolic dysregulation after SCI and warrant confirmation in larger studies. Disclosure A. Alamdari: None. S. Hoekstra: None. A. Gastaldelli: Consultant; Current; Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Other - educational grant; Ended; Boehringer Ingelheim International GmbH. Other - educational grant; Current; Eli Lilly and Company. Consultant; Ended; Merck Sharp & Dohme Corp. Speaker's Bureau; Ended; Merck Sharp & Dohme Corp. Other - grant reviewer; Ended; Pfizer Inc. Advisory Panel; Ended; Novo Nordisk Global Business Services. Speaker's Bureau; Ended; Novo Nordisk Global Business Services. Advisory Panel; Ended; Regeneron Pharmaceuticals Inc. Other - educational grant; Current; Madrigal Pharmaceuticals, Inc. Speaker's Bureau; Ended; Madrigal Pharmaceuticals, Inc. M.E. Trbovich: None. M. Salehi: Advisory Panel; Ended; Vognex. Advisory Panel; Current; Amylyx.