Hypercalcemia is commonly caused by hyperparathyroidism and malignancy. Medication-induced hypercalcemia is less common. Tirzepatide is a dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist (GLP-1/GIP RA) used to aid weight loss and glycemic control. It is associated with gastrointestinal side effects, but its effect on calcium homeostasis has not been well reported. We report the case of a 75-year-old woman with a history of type 2 diabetes, hypertension, obesity, chronic kidney disease, and post-surgical hypothyroidism and hypoparathyroidism, who presented with severe symptomatic hypercalcemia one month after starting tirzepatide while taking bendroflumethiazide, calcium carbonate, and alfacalcidol. Her serum calcium levels had been in the normal treatment range before the initiation of tirzepatide. All other possible causes of hypercalcemia were ruled out. Her calcium levels returned to normal after intravenous fluid therapy and withholding tirzepatide, bendroflumethiazide, and calcium carbonate. This case highlights the potential occurrence of severe hypercalcemia during the concurrent use of tirzepatide with bendroflumethiazide, a calcium supplement, and vitamin D in the context of chronic kidney disease. With the increasing use of tirzepatide, healthcare workers need to be mindful of the interaction between tirzepatide and these potential risk factors. While further research is required, we suggest serum calcium monitoring during similar clinical scenarios.
