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5 Avexitide, a 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 Results in Recurrent, Rapid GLP-1 Receptor and Promotes Glucose Altered Stomach 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 associated with bariatric surgery high insulin levels in the beta cells to inhibit the levels resulting from (e.g., Roux-en-Y gastric bypass) bloodstream, and subsequent effect of exaggerated inhibition of the effect of leads to exaggerated GLP-1 hypoglycemia GLP-1 exaggerated GLP-1 secretion in people with PBH GLP-1=glucagon-like peptide-1

Many also report improvements in energy, mood, blood sugar control, and overall well-being as their bodies adapt to healthier habits

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Mroz PA, Finan B, Gelfanov V et al (2019) Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism

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