Effects of Combined SGLT2 Inhibitor and RAAS Blockade ± Thiazide Therapy on Serum Electrolyte Balance in Type 2 Diabetic Patients: A Retrospective Cohort Study

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are widely used in diabetic patients for their antihyperglycemic and cardioprotective effects. They are frequently co-administered with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and/or thiazide diuretics in clinical practice. However, the combined use of these agents may affect serum electrolyte balance. This study aimed to evaluate the changes in serum sodium, potassium, calcium, magnesium, and phosphorus levels associated with ACEi/ARB ± thiazide therapy and its combination with SGLT2 inhibitors in patients with type 2 diabetes. Methods This retrospective cohort study included 494 adult patients with type 2 diabetes and preserved renal function (eGFR ≥60 mL/min/1.73 m²), who received SGLT2 inhibitors at a tertiary care center between January 2018 and December 2022. Patients were stratified into five groups based on their antihypertensive and antidiabetic medication combinations. Electrolyte levels were recorded before and six weeks after treatment initiation. Intragroup comparisons were performed using the Wilcoxon signed-rank test, and a p-value <0.05 was considered statistically significant. Results SGLT2 inhibitor monotherapy was associated with a significant increase in serum sodium (p = 0.034) and magnesium (p = 0.004) levels. In the ACEi/ARB + SGLT2-i group, post-treatment magnesium (p = 0.001) and phosphorus (p = 0.003) levels were significantly elevated. The triple therapy group (ACEi/ARB + thiazide + SGLT2-i) also showed a significant rise in magnesium levels (p = 0.002). ACEi/ARB monotherapy led to an increase in potassium (p = 0.043) and phosphorus (p = 0.020) levels, whereas the addition of SGLT2-i mitigated the potassium rise. No significant changes in calcium levels were observed in most groups, except a mild increase with thiazide use alone. Conclusions The use of SGLT2 inhibitors in combination with ACEi/ARB ± thiazide diuretics appears to be safe in terms of electrolyte balance and may even provide a stabilizing effect, particularly for serum potassium and magnesium levels. Further prospective studies are needed to confirm these findings and to explore their clinical implications in diabetic patients on multidrug regimens. Trial registration Not applicable.