The impact of sodium-glucose co-transporter-2 inhibitors on serum sodium and potassium in patients with Heart Failure: a systematic review and meta-analysis

Abstract

Background Managing electrolyte abnormalities, particularly sodium and potassium, in patients with heart failure (HF) remains a concern. A novel anti-diabetic drug, sodium-glucose co-transporter-2 (SGLT2) inhibitors, has become suitable for HF patients, improving cardiovascular outcomes. Therefore, we aimed to conduct a meta-analysis to evaluate the effect of SGLT2 inhibitors on serum sodium and potassium. Methods We systematically searched five databases, identifying randomized clinical trials (RCTs) reporting changes in serum sodium and potassium levels with SGLT2 inhibitors compared to comparator groups. Outcomes were presented as weighted mean differences (WMD) and standardized MD (SMD) with 95 confidence intervals (CI). Subgroup and sensitivity analyses were also conducted. Results 13 studies were included, with 13 studies with 10,617 participants reporting on serum sodium and nine studies with 9877 participants on serum potassium. In acute HF, SGLT2 inhibitors did not significantly affect serum sodium (WMD: 1.21 mmol/L; 95 CI: - 0.79, 3.21) or potassium levels (WMD: 0.11 mEq/L; 95 CI: - 0.20, 0.42). Subgroup analyses suggested possible variations by follow-up duration (< 7 days vs. >= 30 days) and drug type, but findings remained non-significant. Sensitivity analysis using the leave-one-out method and risk of bias assessment results showed no considerable changes in the statistical significance of the pooled results. Similarly, in chronic HF, no significant differences were observed for serum sodium (WMD: 0.23 mmol/L; 95 CI: - 0.45, 0.91) or potassium (WMD: 0.07 mEq/L; 95 CI: - 0.29, 0.44). Sensitivity and subgroup analyses based on duration, drug type, diabetes status, renal function, or systolic blood pressure did not reveal clinically meaningful differences across all analyses. For all analyses, Egger's test was non-significant, indicating no strong evidence of small-study effects. Moreover, the trim-and-fill method combined with the funnel plot did not identify any missing studies, and the recalculated effect size remained unchanged. Conclusions SGLT2 inhibitors did not significantly alter serum sodium or potassium levels in acute or chronic HF, suggesting that these drugs can be safe regarding electrolyte disturbances. Additional RCTs are warranted to enhance the robustness of evidence regarding the mechanisms and effects of SGLT2 inhibitors on serum electrolyte levels, considering variations across different types of SGLT2 inhibitors.