Tirzepatide Linked to Ketoacidosis in Non-Diabetic, Non-Obese Individual
Background
Diabetic ketoacidosis (DKA) is a serious complication of diabetes characterized by high blood sugar, high ketone levels, and acidic blood. While GLP-1 receptor agonists like tirzepatide (a dual GLP-1/GIP agonist) are highly effective for managing type 2 diabetes and obesity, they are rarely associated with DKA, typically in individuals with underlying diabetes. This case report addresses the critical knowledge gap regarding tirzepatide-induced ketoacidosis occurring in a nonobese individual without a prior diagnosis of diabetes.
Results
After four weeks on 5 mg weekly of tirzepatide, the patient presented with severe nausea, vomiting, and profound fatigue, leading to emergency hospital admission. Initial laboratory tests revealed a blood glucose level of 185 mg/dL, a serum pH of 7.28 (normal range 7.35-7.45), and a bicarbonate level of 14 mEq/L (normal range 22-29 mEq/L). Crucially, serum ketone levels were significantly elevated at 4.8 mmol/L (normal <0.6 mmol/L), confirming a diagnosis of euglycemic ketoacidosis. The patient exhibited severe metabolic acidosis with a pH of 7.28 and significantly elevated ketone levels at 4.8 mmol/L, confirming tirzepatide-induced ketoacidosis despite non-diabetic glucose levels. Upon discontinuation of tirzepatide and initiation of intravenous fluids and insulin, the patient's symptoms rapidly improved, with ketone levels normalizing within 48 hours and pH returning to 7.39 within 72 hours. No other identifiable causes for the ketoacidosis were found after extensive investigation, strongly implicating tirzepatide.
Why It Matters
This case report highlights a rare but serious adverse event associated with tirzepatide use, particularly in individuals without pre-existing diabetes or obesity. Clinicians must be vigilant for symptoms of ketoacidosis in all patients receiving tirzepatide, even those prescribed off-label for weight management. This finding suggests a critical need for enhanced patient education and monitoring protocols, potentially leading to updated prescribing guidelines and warnings for GLP-1/GIP agonists. Further research, including larger observational studies or post-marketing surveillance, is warranted to better understand the incidence and risk factors for this adverse event.