Dynamic trajectories of electrolytes and bone metabolism with tofogliflozin and glimepiride: A post-hoc analysis

Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors influence electrolyte balance and bone metabolism. However, their effects in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes remain unclear. Methods 40 participants with type 2 diabetes and MASLD were randomly assigned to tofogliflozin (20 mg/day) or glimepiride (0.5–6.0 mg/day) for 48 weeks. Changes in anthropometric measures, electrolytes, and bone metabolism markers were evaluated. Results Tofogliflozin significantly increased serum magnesium (2.0 ± 0.19 to 2.13 ± 0.18 mg/dL) and transiently elevated serum calcium (9.15 to a maximum of 9.60 mg/dL) and tartrate-resistant acid phosphatase 5b (283.5 to 352.0 mU/dL). It also transiently reduced serum potassium (4.05 ± 0.31 to 3.89 ± 0.21 mEq/L) and uric acid (5.10 to a minimum of 4.55 mg/dL), accompanied by increased urinary potassium excretion and fractional uric acid excretion. Urinary magnesium and calcium excretion did not change significantly. In the tofogliflozin group, reductions in steatosis and hepatocellular ballooning scores were significantly correlated with increases in serum type I collagen cross-linked N-telopeptide. Conclusions Tofogliflozin modified electrolyte profiles and transiently influenced bone turnover markers. The observed correlations suggest a potential association between improvements in hepatic histology and changes in bone metabolism during SGLT2 inhibitor therapy.