SGLT2 inhibitors increase low serum magnesium levels in patients with chronic kidney disease immediately after treatment

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown in clinical trials to increase serum Mg²⁺ levels in patients with type 2 diabetes mellitus. However, it is unclear whether this effect is similarly observed in patients with chronic kidney disease (CKD) and whether such an increase is observed immediately after treatment.

Our retrospective observational study included the 62 patients with CKD who started SGLT2 inhibitor therapy at our institution between 2017 and 2022 and who had complete data on serum Mg²⁺ measurements at baseline and at 1, 3, and 6 months after treatment. Patients were divided into three subgroups, stratified by serum Mg²⁺ levels at baseline. We evaluated the changes in serum Mg²⁺ levels from baseline to 6 months after treatment and the factors associated with these changes.

Median eGFR and mean serum Mg²⁺ at baseline were 33.5 mL/min/1.73 m² and 2.03 mg/dL, respectively. Treatment with SGLT2 inhibitors significantly increased serum Mg²⁺ levels immediately from 1 month after treatment compared with those at baseline and persisted over 6 months, with an overall mean change of 0.13 mg/dL from baseline to 6 months. This increased effect was observed in the low and middle tertile subgroups, but not in the high tertile subgroup. Multivariate linear regression analysis revealed that baseline serum Mg²⁺ levels and sodium-chloride differences, as a parameter of acid–base status, were independently associated with these changes.

SGLT2 inhibitors increased serum Mg²⁺ levels in patients with CKD, particularly those with lower baseline Mg²⁺ levels, potentially improving their prognosis.