Sodium - Glucose Cotransporter 2 Inhibitors and Management of Refractory Hypomagnesemia Without Overt Urinary Magnesium Wasting: A Report of 2 Cases

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitor have become widely used in patients with diabetes, heart failure, and kidney disease to improve clinical outcomes and diminish hospitalizations. They have also been associated with increased serum magnesium levels in patients with type 2 diabetes. The use of SGLT2 inhibitors resulted in improved magnesium homeostasis in a series of patients with refractory hypomagnesemia with urinary magnesium wasting. However, the role of SLGT2 inhibitors in patients with hypomagnesemia without urinary magnesium wasting remains unexplored. We report 2 cases with refractory hypomagnesemia without significant urinary magnesium wasting and dramatically improved serum magnesium levels after the initiation of SGLT2 inhibitors. Case 1 achieved independence from weekly intravenous magnesium infusions and reached sustainably greater serum magnesium levels with decreased oral magnesium supplementation and increased urinary fractional excretion of magnesium. Case 2 demonstrated improved serum magnesium levels with reduced oral magnesium supplementation without significant reduction in urinary fractional excretion of magnesium. These findings not only expand the use of SGLT2 inhibitors but also open the door for further studies to better understand the pathophysiology of how magnesium homeostasis is altered with inhibition of SGLT2.

Keywords: Empagliflozin; SGLT2 inhibitors; hypomagnesemia; magnesium; type 2 diabetes.

Figure 1

Case 1. Historical serum magnesium levels with respect to before and after initiation of empagliflozin. The solid blue background represents a period of dependence on intravenous magnesium sulfate (IV MgSO₄), varying from once a week to twice a month dosing. The empty white background represents independence from IV MgSO₄. The dashed line at serum magnesium level of 1.7 mg/dL represents a lower limit of normal.

Figure 2

A comparison of serum magnesium levels (A), fractional excretion of magnesium (FEMg) (B), 24-hour urine magnesium levels (C), and supplemental dose of oral magnesium supplements (D) before and after initiation of empagliflozin. The solid red line represents average magnesium levels for respective columns. The dashed line at serum magnesium level of 1.7 mg/dL represents a lower limit of normal. Note: Patient 1 was dependent on intravenous magnesium sulfate infusions, which were discontinued after initiation of empagliflozin. Abbreviation: SGLT2, sodium-glucose cotransporter 2.