SGLT2 Inhibitors in Management of Severe Hypomagnesemia in Patients Without Diabetes: A Report of 4 Cases

Abstract

Sodium/glucose cotransporter 2 (SGLT2) inhibitors have demonstrated a class effect in improving serum magnesium levels in patients with diabetes. Additionally, recent reports have shown their promising beneficial effects in the treatment of refractory hypomagnesemia in patients with diabetes. However, their role in treating hypomagnesemia in patients without diabetes remains unexplored. Here, we report 4 cases of severe and refractory hypomagnesemia that showed dramatic improvement after initiating SGLT2 inhibitors in patients without diabetes. Case 1 had calcineurin inhibitor-associated severe hypomagnesemia. Cases 2, 3, and 4 had refractory hypomagnesemia associated with platinum-based chemotherapy with or without gastrointestinal losses. Case 1 was able to withdraw from high-dose oral magnesium supplementation. Cases 2 and 3 achieved independence from intravenous magnesium supplementation, whereas case 4 had decreased intravenous magnesium requirements. All the cases demonstrated sustainably improved serum magnesium levels. Withdrawal of SGLT2 inhibitors in case 4 resulted in worsening serum magnesium levels and intravenous magnesium requirements. The extraglycemic benefit of this group of medications not only suggests the need for further studies to better understand the effect of SGLT2 inhibitors on magnesium homeostasis but also supports expanded use in a larger patient population.

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

Figure 1

Sodium/glucose cotransporter 2 (SGLT2) inhibition was associated with increased serum magnesium levels in case 1 (1.60 ± 0.24, n=15 vs 1.79 ± 0.079, n=12; P = 0.02), case 2 (1.54 ± 0.16, n=20 vs 2.0 ± 0.28, n=18; P < 0.001), case 3 (1.25 ± 0.17, n=14 vs 1.67 ± 0.16, n=11; P < 0.001) and case 4 (1.52 ± 0.07, n=10 vs 1.95 ± 0.19, n=10; P <0.001). SGLT2 inhibition was associated with a decrease in oral magnesium supplementation in case 1 (672 mg vs 0 mg) and case 2 (162 mg vs 108 mg), allowed withdrawal from intravenous magnesium sulfate (IV MgSO₄) dependence in case 2 and case 3, and decreased the need for IV MgSO4 supplementation in case 4. Withdrawal of SGLT2 inhibition in case 4 was associated with a decrease in serum magnesium levels (1.95 ± 0.19, n=10 vs 1.59 ± 0.10, n=12; P < 0.001) and an increase in requirements for IV MgSO₄ (12 gm vs 20 gm IV MgSO₄ at 1 month pre- vs post-SGLT2i withdrawal, respectively). Abbreviations: IV MgSO₄, intravenous magnesium sulfate; SGLT2i, sodium-glucose cotransporter 2 inhibitor; oral Mg, oral elemental magnesium.