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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

The characteristics of heart rate increase appear to be: Dose-dependent : Higher doses generally produce greater increases Agent-specific : Some GLP-1 receptor agonists may have more pronounced effects than others Time-dependent : Heart rate changes typically occur early in treatment and may stabilise over time Clinically modest : The absolute increase is generally small and within normal physiological variation Proposed mechanisms for heart rate elevation include modulation of autonomic nervous system activity, with potential reduction in parasympathetic (vagal) tone or increase in sympathetic activity

Impact of precursor-derived peracetic acid on post-weaning diarrhea, intestinal microbiota, and predicted microbial functional genes in weaned pigs