SGLT2 Inhibitors: Unlocking the Solution for Refractory Hypomagnesemia in Suspected Gitelman Syndrome

Introduction: Hypomagnesemia is a rare and poorly understood magnesium (Mg+) disorder, often resistant to conventional therapies. Emerging studies suggest sodium-glucose cotransporter 2 inhibitors (SGLT2i) may help. We present a case of complex refractory hypomagnesemia with suspected Gitelman Syndrome successfully treated with SGLT2 inhibitors. Case Description: A 70-year-old woman with PMH of CKD stage 2, DM T2, HTN presented with chronic severe hypomagnesemia & frequent muscle cramps. She was on Pantoprazole & HCTZ for >7 years, discontinued 1 year before presentation. Workup as follows: Na+ 140 mmol/L, K+ 3.4 mmol/L, CO2 27 mmol/L, BUN 8 mg/dL, Creatinine 0.8 mg/dL, Glucose 205 mg/dL, Ca+ 9.9 mg/dL, & Mg+ ranging between 1.0 to 1.3 mg/dl. 24-hour urine lytes: Mg+ 59.4 mg, Ca+ 68 mg/dL, K+ 50 mmol, Na+ 90 mmol. Creatinine 0.8 g. Fractional excretion (FE) of Ca+ 0.01% & Mg+ 6.9%. Suspected a case of Gitelman Syndrome (genetic test pending) and initially started on oral Mg+ as well as Mg+ IV infusion (4g/4 weeks), which was later increased to 4g weekly for 4 weeks with maintenance at 4g-biweekly. Due to the refractory nature, she started on an SGLT2i (Empagliflozin 10 mg daily), resulting in dramatic improvement & stable Mg+ levels (>2.0 mg/dl) without any further infusion. Interestingly, three of her four children also developed low magnesium after age of 50, requiring supplements, currently under investigation. Discussion: To the best of our knowledge, this is the first reported case of Gitelman treated with SGLT2i. Studies suggest SGLT2i can improve magnesium homeostasis, especially in diabetic patients. Possible mechanisms include glycemic control with magnesium redistribution and enhanced intestinal absorption/renal resorption via TRPM6-medicated transport. Further research is needed to define the role of SGLT2i in treating hypomagnesemia & its inclusion in treatment guidelines for refractory cases.