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Avexitide, an Investigational, First-in-Class GLP-1 Receptor Antagonist, Targets a Central Pathway of PBH Pathophysiology GLP-1 Receptor Antagonism 1 2 3 4 Hypersecretion of Insulin Avexitide Binds to Mitigates Insulin Hypersecretion Altered Stomach Results in Recurrent, Rapid GLP-1 Receptor and Promotes Glucose Drops in Blood Glucose Stabilization Insulin Pancreas GLP-1 Islet Insulin Beta Cells Receptor Intestine Stable Blood Meal Meal GLP-1 Glucose Response +10x increase Avexitide in GLP-1 Rapid Drop in Blood Glucose levels TIME TIME Altered nutrient transit This exaggerated GLP-1 Avexitide binds to the GLP-1 Decreased insulin secretion due to anatomical changes secretion leads to abnormally receptor on pancreatic islet and stabilized glucose levels associated with bariatric surgery high insulin levels in the beta cells to reduce the resulting from inhibition of the (e.g., Roux-en-Y gastric bypass) bloodstream, and subsequent effects of excessive effect of exaggerated GLP-1 leads to exaggerated GLP-1 hypoglycemia GLP-1 signaling secretion in people with PBH GLP-1=glucagon-like peptide-1