The Effects of Sodium-glucose Cotransporter 2 Inhibitors on Serum Sodium in Patients With Type 2 Diabetes

Key Points – Sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with a reduced prevalence of hyponatremia and a lower risk of hospitalizations because of hyponatremia. SGLT2 inhibitors were associated with a reduced prevalence of hypernatremia and a lower risk of hospitalizations because of hypernatremia. SGLT2 inhibitors could serve as a therapeutic option for patients with hyponatremia and potentially lower health care costs caused by it. Background – To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the prevalence, severity, and complications of hyponatremia and hypernatremia in diabetic patients using real-world data, compared with dipeptidyl peptidase 4 (DPP4) inhibitors.Methods – This was a retrospective cohort study, and the dataset was sourced from the data repositories of Clalit Health Services. From January 1, 2016, through December 31, 2021, we identified diabetic patients who received SGLT2 inhibitors, comparing them with a propensity matched control group treated with DPP4 inhibitors. The coprimary end points were a composite outcome of the prevalence of severe hyponatremia and hospitalizations because of hyponatremia and the prevalence of moderate hypernatremia and hospitalizations because of hypernatremia.Results – The study included 22, 686 patients, with 11, 343 receiving SGLT2 inhibitors and an equal number treated with DPP4 inhibitors. A significant reduction in the risk of the hyponatremia primary composite outcome was observed in patients treated with SGLT2 inhibitors (hazard ratio [HR], 0.60; 95% confidence intervals [CI], 0.53 to 0.69), as well as in the risk of the hypernatremia composite primary with a HR of 0.54 (95% CI, 0.44 to 0.63), compared with DPP4 inhibitors. In addition, the risk of hospitalizations because of hyponatremia and hypernatremia was significantly lower in the SGLT2 inhibitor group (HR, 0.64; 95% CI, 0.54 to 0.74; P < 0.001; and HR, 0.55; 95% CI, 0.36 to 0.74; P = 0.002; respectively).Conclusions – SGLT2 inhibitors were associated with a reduced prevalence of hyponatremia and a lower risk of hyponatremia-related hospitalizations compared with DPP4 inhibitors in patients with diabetes.