Hypomagnesemia-Induced Hypocalcemia Successfully Treated With Sodium-Glucose Cotransport Inhibitor (SGLT-2i), a Case Report

Abstract

Background: Severe hypomagnesemia can result in hypocalcemia as magnesium is a co-factor necessary for PTH production in the parathyroid glands. Calcium replacement alone can prove difficult in the setting of hypomagnesemia, therefore optimal treatment should also include repletion and normalization of magnesium levels. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are a class of oral medications used in the treatment of type 2 diabetes and recently in heart failure which inhibit the sodium-glucose transporter in the proximal tubule of the kidney. A lesser known effect of SGLT-2i is renal tubular resorption of magnesium leading to increased serum magnesium levels. We report a case of refractory diuretic-induced hypomagnesemia and subsequent hypocalcemia which was successfully treated with SGLT-2i. Clinical Case: A 74-year-old male with uncontrolled type 2 DM, vitamin D deficiency, NASH cirrhosis, chronic lower extremity edema on furosemide therapy, and CKD stage III presented with unexplained hypocalcemia at 7.4–8.4 mg/dL (n: 8.8 – 10.4 mg/dL) and hypomagnesemia at 1.0–1.3 mg/dL (n: 1.5 – 2.5 mg/dL) for the past two years. He had been followed by his PCP who performed a workup revealing 25-OH vitamin D level 22.6 ng/mL, PTH 43 pg/mL (n: 10–55 pg/mL) with corresponding calcium 8.1 mg/dL. He was started on ergocalciferol 50,000IU, magnesium oxide 400mg daily, titrated up to 400mg BID, and calcium carbonate 400mg BID with no improvement in magnesium or calcium level. Later, he was admitted to the hospital with volume overload. During admission, magnesium was repleted with IV magnesium sulfate to a level of 2.1 mg/dL and serum calcium level normalized to 8.8 mg/dL without supplementation once magnesium level was replete. He was discharged with resumption of oral magnesium sulfate 400mg BID, but within 10 days his serum magnesium level dropped to 1.0 mg/dL. Endocrinology was consulted, and due to the severe hypomagnesemia, empagliflozin 10mg daily was started for the purpose of increasing the serum magnesium level and secondarily for improvement in glucose and edema control. After one week of treatment, the magnesium level increased to 1.4mg/dL and calcium level to 8.7mg/dL. Six months later, magnesium and calcium levels remained stable at 1.7 mg/dL and 9.1 mg/dL, respectively. The patient continues to now remain normocalcemic and normomagnesemic on empagliflozin 12.5mg daily. Conclusion: SGLT-2i represent a potent class of anti-hyperglycemic agents with the secondary effect of renal tubular absorption of magnesium which may help achieve appropriate PTH secretion in cases of treatment refractory hypocalcemia. This is one of the first cases to report the off-label use of SGLT-2i for refractory hypocalcemia due to hypomagnesemia. SGLT-2i should be considered in these cases especially in the setting of suboptimally controlled type 2 DM when other interventions have been unsuccessful.