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Does Incretin Agonism Have Sustainable Efficacy

Established risk factors include: History of pancreatitis: Patients with prior episodes face substantially higher recurrence risk and require careful consideration before initiating GLP-1 therapy Gallstone disease: Cholelithiasis and biliary sludge can precipitate pancreatitis, particularly during periods of rapid weight loss Hypertriglyceridemia: Triglyceride levels 1,000 mg/dL significantly increase pancreatitis risk, with risk beginning to rise at levels 500 mg/dL Excessive alcohol consumption: Alcohol remains one of the most common pancreatitis triggers and may interact with metabolic changes induced by GLP-1 medications Obesity and rapid weight loss: While weight reduction is therapeutic, very rapid loss may increase gallstone formation Warning signs of acute pancreatitis that patients should recognize include severe, persistent abdominal pain, typically in the upper abdomen and often radiating to the back

Topical bioavailability: Lower but meaningful

USA 116 , 47384743 (2019)

The tradeoff is real