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The most important serious side effects include acute pancreatitis (severe persistent abdominal pain radiating to the back, though clinical trials found similar pancreatitis rates to comparators), severe dehydration from persistent vomiting or diarrhea (signs include dizziness, decreased urination, extreme thirst), gallbladder disease including cholecystitis or cholelithiasis (right upper quadrant pain, fever, jaundice), severe allergic reactions (difficulty breathing, swelling of face or throat), and severe hypoglycemia when combined with insulin or sulfonylureas (confusion, loss of consciousness, seizures)
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In the subsequent years, several observational studies have yielded conflicting results.4043 Notably, most of the available information is drawn from the subgroup of exendin-4-based drugs, which differ structurally from human GLP-1
A paper published in early 2026 reviewed 12 clinical trials that had incorporated nutritional interventions or dietary assessments during semaglutide or tirzepatide therapy in adults with obesity or Type 2 diabetes
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