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

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 utilizing real-world data, compared to dipeptidyl peptidase 4 (DPP4) inhibitors. Methods: Retrospective cohort study, 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 co-primary endpoints were a composite outcome of the prevalence of severe hyponatremia and hospitalizations due to hyponatremia, and the prevalence of moderate hypernatremia and hospitalizations due to 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 (HR 0.60, 95% CI 0.53–0.69), as well as in the risk of the hypernatrmia composite primary with a HR of 0.54 (95%, CI 0.44–0.63), compared to DPP4 inhibitors. Additionally, the risk of hospitalizations due to hyponatremia and hypernatremia was significantly lower in the SGLT2 inhibitor group (HR 0.64, 95% CI 0.54–0.74, p < .001; HR of 0.55 95% CI 0.36–0.74, p = 0.002, respectively). Conclusions: SGLT2 inhibitors were associated with a reduced prevalence of hyponatremia and a lower risk of hyponatremia-related hospitalizations compared to DPP4 inhibitors in patients with diabetes.