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Introduction: Previous studies have reported that sodium-glucose co-transporter 2 (SGLT2) inhibitors affect serum electrolytes levels, especially magnesium. This study aims to integrate direct and indirect trial evidence to evaluate the relative effects of all SGLT2 inhibitors against each other on electrolyte levels in patients with type 2 diabetes (T2D).

Methods: Electronic databases were systematically searched through December 2018 to identify eligible randomized controlled trials (RCTs) that reported mean changes in serum electrolyte levels, including magnesium, sodium, potassium, phosphate, calcium, and urate in patients with T2D. Random-effects pairwise and network meta-analyses were performed to calculate the weighted mean difference (WMD) before and after SGLT2 treatment.

Results: Twenty-four RCTs involving 17,820 patients with five SGLT2 inhibitors were included. Compared with placebo, SGLT2 inhibitors were significantly associated with elevations in serum magnesium by 0.08 mmol/L and serum phosphate by 0.03 mmol/L, and significantly associated with decreases in serum urate by 37.62 umol/L. Our network meta-analysis showed significant increases in serum magnesium among the patients taking canagliflozin (WMD = 0.08 mmol/L), dapagliflozin (WMD = 0.08 mmol/L), empagliflozin (WMD = 0.06 mmol/L), and ertugliflozin (WMD = 0.06 mmol/L) compared to placebo. No statistically detectable differences were evident between any two of SGLT2 inhibitors.

Discussion: SGLT2 inhibitors could significantly increase serum magnesium, indicating a potentially similar class-effect. However, more data for long-term efficacy and safety of raising serum magnesium and phosphate in T2D patients with different clinical phenotypes are needed for further investigation.