Tirzepatide and Calcium Supplementation Linked to Symptomatic Hypercalcemia in 70-Year-Old Female

Type 2 diabetes mellitus and obesity are prevalent conditions for which tirzepatide, a dual GLP-1R and GIPR agonist, is an effective treatment. While common adverse effects include gastrointestinal symptoms, pancreatitis, and acute kidney injury, hypercalcemia is a rarely reported complication. Previous instances of hypercalcemia with GLP-1R agonists have involved concomitant thiazide diuretics or exogenous calcium supplementation, highlighting a potential interaction. This case addresses a gap by describing hypercalcemia specifically with tirzepatide and calcium, suggesting a novel interaction mechanism.

This case report details the clinical course of a 70-year-old female with a history of obstructive sleep apnea, osteoporosis (managed with calcium supplements), and obesity. She had been initiated on tirzepatide approximately three months prior to presenting with nausea and vomiting. The patient's medical history, current medications, and presenting symptoms were thoroughly documented. Subsequent laboratory analyses were performed to evaluate her electrolyte balance, renal function, and other metabolic parameters, leading to the diagnosis of symptomatic hypercalcemia and associated complications.

Upon presentation, the patient exhibited symptomatic moderate hypercalcemia, accompanied by hypokalemia, metabolic alkalosis, and acute kidney injury. The patient's hypercalcemia was symptomatic, presenting with nausea and vomiting.

The patient's hypercalcemia, hypokalemia, metabolic alkalosis, and acute kidney injury all corrected after intravenous hydration. This correction suggests a direct link between her clinical presentation and the electrolyte imbalance. The authors hypothesize the mechanism most likely involves tirzepatide's effect on bone turnover combined with concomitant increased calcium absorption from her ongoing calcium supplement ingestion. This is the first reported instance of hypercalcemia specifically attributed to tirzepatide use alongside calcium supplementation, distinguishing it from prior reports involving other GLP-1R agonists.