Hypercalcemia Induced by Tirzepatide and Calcium Supplementation: A Case Report

Tirzepatide is a glucagon-like peptide-1 receptor (GLP-1R) agonist and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist that is used for diabetes mellitus and weight loss. Common adverse effects include gastrointestinal symptoms such as nausea and vomiting, pancreatitis, and acute kidney injury. Hypercalcemia is rarely reported in the literature and has previously been reported in patients taking GLP-1R agonists with concomitant thiazide diuretic or exogenous calcium supplement. We report a 70-year-old female with obstructive sleep apnea started on tirzepatide three months prior to presentation, osteoporosis on calcium supplements, and obesity, who developed nausea and vomiting. She was found to have symptomatic moderate hypercalcemia with hypokalemia, metabolic alkalosis, and acute kidney injury that corrected after intravenous hydration. No prior literature describes hypercalcemia from tirzepatide use and calcium supplementation. The mechanism most likely involves tirzepatide's effect on bone turnover and concomitant increased absorption from calcium supplement ingestion. Clinicians need to closely monitor patients' electrolytes, especially calcium, when initiating patients on tirzepatide. Further research is warranted to reveal tirzepatide's mechanism regarding calcium metabolism.