SGLT2 Inhibitors for Treatment of Refractory Hypomagnesemia: A Case Report of 3 Patients

Abstract

In patients with urinary magnesium wasting, oral and intravenous supplementation often fail to adequately improve serum magnesium levels. Glucose intolerance and diabetes mellitus frequently accompany hypomagnesemia. Clinical trials examining inhibitors of the type 2 sodium glucose cotransporter (SGLT2) show small but significant increases in serum magnesium levels in diabetic patients. This report describes dramatic improvement in serum magnesium levels and associated symptoms after initiating SGLT2 inhibitor therapy in 3 patients with refractory hypomagnesemia and diabetes. Each patient received a different SGLT2 inhibitor: canagliflozin, empagliflozin, or dapagliflozin. One patient discontinued daily intravenous magnesium supplements and exhibited higher serum magnesium levels than had been achieved by magnesium infusion. 2 of the 3 patients exhibited reduced urinary fractional excretion of magnesium, suggesting enhanced tubular reabsorption of magnesium. These observations demonstrate that SGLT2 inhibitors can improve the management of patients with otherwise intractable hypomagnesemia, representing a new tool in this challenging clinical disorder.

Keywords: Magnesium; SGLT2 inhibitors; canagliflozin; dapagliflozin; diabetes; empagliflozin; hypomagnesemia; type 2 diabetes.

Figure 1

Sodium glucose cotransporter 2 (SGLT2) inhibition was associated with improved hypomagnesemia and reduction in fractional excretion of magnesium (FE_Mg) in 2 of 3 patients. (A) Serum magnesium levels on SGLT2 inhibitor (SGLT2i) therapy are compared with magnesium levels before initiation of these agents. To convert mg/dL to mmol/L, divide by 2.43. (B) FE_Mg before and after initiation of treatment with an SGLT2i. FE_Mg was calculated as 100 ∙ (uMg ∙ sCr)/(0.7 ∙ sMg ∙ uCr), where uMg and uCr represent urinary magnesium and creatinine concentrations measured in 24-hour urine collections and sMg and sCr represent serum magnesium and creatinine levels, respectively. Dashed line at 4% represents upper limit of normal. SGLT2 inhibition was associated with decreased FE_Mg in patient 1 (32% ± 3%, n = 4 before vs 22% ± 2.5%, n = 2 on the drug; P = 0.02) and patient 3 (20% ± 9%, n = 14 before vs 11% ± 1%, n = 8 on the drug; P = 0.01), but not patient 2 (13% ± 4%, n = 3 before vs 13% ± 1%; n = 2, on empagliflozin). Abbreviation: IV Mg²⁺, daily intravenous magnesium supplementation.