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The Core GLP-1 Mechanism GLP-1 Pathway Simplified Meal Intake Intestinal L-cells release GLP-1 GLP-1 binds GLP-1 receptors cAMP signaling Activation of PKA + PI3K/Akt pathways Multiple metabolic benefits Practical Clinical Effects In the Pancreas Insulin secretion from -cells Glucagon secretion from -cells Preservation of -cell mass Reduced -cell apoptosis In the Brain Appetite suppression Satiety enhancement Reduced food cravings In the Gastrointestinal Tract Delayed gastric emptying Reduced postprandial glucose spikes In Peripheral Tissues Improved glucose uptake Enhanced insulin sensitivity Reduced hepatic gluconeogenesis Evolution of GLP-1 Therapy: Historical Milestones Current Era Emergence of: Oral GLP-1 drugs Dual agonists Triple agonists Small-molecule GLP-1 therapies Current GLP-1 Agents Short-Acting Exenatide Lixisenatide Long Acting Liraglutide Dulaglutide Semaglutide Oral GLP-1 Oral semaglutide Orforglipron (new generation oral small-molecule GLP-1RA) Dual Agonists Tirzepatide (GLP-1 + GIP) Triple Agonists Retatrutide (GLP-1 + GIP + glucagon receptor) These newer agents are redefining obesity medicine and cardiometabolic care

12 GLP-1RAs acutely increase dopamine signaling in the VTA, which could cause acute pleasure and euphoria

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