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Contact your healthcare provider immediately if thirst is accompanied by: Signs of severe dehydration (dark urine, dizziness, confusion, rapid heartbeat, decreased skin turgor) Persistent vomiting or diarrhea lasting more than 24 hours Inability to keep fluids down Symptoms of diabetic ketoacidosis (fruity breath odor, rapid breathing, abdominal pain) Blood glucose readings consistently above 250 mg/dL (check ketones if available) Blood glucose readings below 70 mg/dL with symptoms of hypoglycemia Decreased urine output despite drinking fluids Rapid weight loss over 24-48 hours (suggesting dehydration) While tirzepatide does not require dose adjustment based on renal function, patients experiencing severe gastrointestinal adverse reactions should be monitored for acute kidney injury, particularly if dehydration occurs

GIPR activation potentiates glucose-dependent insulin release and has more recently been shown to modulate adipose-tissue lipid handling and central appetite pathways