The Use of Amiloride and Sodium-Glucose Cotransporter 2 Inhibitors in Cisplatin-Induced Hypomagnesemia: A Case Report and Review of the Literature

Cisplatin, a chemotherapy agent widely used since its FDA approval in 1978 for testicular cancer, is associated with nephrotoxicity and hypomagnesemia. Magnesium supplementation is not only a treatment for hypomagnesemia but also a well-established agent in preventing cisplatin-induced nephrotoxicity (CIN). Considering the challenges associated with intravenous magnesium use and even with the supplementation of oral forms, there is a need for drugs that effectively reduce urinary magnesium excretion. Amiloride and sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have emerged as potential candidates. Amiloride is a well-known potassium-sparing diuretic that also has a hypomagnesemia effect seen in preclinical data. SGLT2 inhibitors are a drug class initially used in diabetes that was also observed to have positive effects on cardiovascular mortality, diabetic kidney disease, and hypomagnesemia. SGLT2 inhibitors were found to reduce hypomagnesemia in a meta-analysis study of 18 trials. However, these trials were not specifically designed for the evaluation of hypomagnesemia, and their current use in hypomagnesemia is considered off-label.