Sodium/Glucose Cotransporter 2 Inhibitors and Magnesium Homeostasis: A Review

Magnesium (Mg²⁺), also known as "the forgotten ion," is the second most abundant intracellular cation and is essential in a broad range of intracellular physiological and biochemical reactions. Its deficiency, hypomagnesemia (Mg²⁺<1.8mg/dL), is a prevalent condition and routinely poses challenges in its management in clinical practice. Sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a new class of drugs with treating hypomagnesemia as their unique extraglycemic benefit. The beneficial effect of SGLT2 inhibitors on magnesium balance in patients with diabetes with or without hypomagnesemia has been noted as a class effect in recent meta-analysis data from randomized clinical trials. Some reports have demonstrated their role in treating refractory hypomagnesemia in patients with or without diabetes. Moreover, studies on animal models have attempted to illustrate the effect of SGLT2 inhibitors on Mg²⁺homeostasis. In this review, we discuss the current evidence and possible pathophysiological mechanisms, and we provide directions for further research. We conclude by suggesting the effect of SGLT2 inhibitors on Mg²⁺homeostasis is a class effect, with certain patients gaining significant benefits. Further studies are needed to examine whether SGLT2 inhibitors can become a desperately needed novel class of medicines in treating hypomagnesemia.