Prevalence of Admission Hyponatremia in Patients With Diabetes Treated With and Without an SGLT2 inhibitor

CONTEXT: Hyponatremia often reflects a free water excess. Sodium/glucose cotransporter 2 (SGLT2) inhibitors increase free water excretion through glucose-induced osmotic diuresis. In 2 randomized double-blind, placebo-controlled trials in patients with the syndrome of inappropriate antidiuresis (SIAD), we showed that empagliflozin increased plasma sodium concentration more effectively than placebo. OBJECTIVE: We hypothesized that long-term therapy with SGLT2 inhibitors might reduce the prevalence of hyponatremia on hospital admission. METHODS: In this retrospective analysis, we extracted data from adult patients with type 2 diabetes (T2DM) hospitalized at the University Hospital Basel between 2015 and 2020. Patients with an SGLT2 inhibitor on admission were matched 1:1 according to age, gender, diagnosis of heart failure, and principal diagnosis to patients without an SGLT2 inhibitor on admission. The primary outcome was the prevalence of hyponatremia (plasma sodium concentration corrected for glycemia <135 mmol/L) on admission. RESULTS: We analyzed 821 patients with T2DM treated with and 821 patients with T2DM without an SGLT2 inhibitor on admission. Hyponatremia prevalence on admission was 9.9% in the treated group, and 8.9% in the matched control group (P = .554), in other words, the risk for hyponatremia did not differ (multivariable adjusted odds ratio 1.08, 95% CI 0.72-1.44, P = .666). There was no difference in the median (interquartile range) plasma sodium concentration between the groups (treated 140 mmol/L [138-142], controls 140 mmol/L [138-142]; P = .1017). CONCLUSION: Based on these retrospective findings, treatment with SGLT2 inhibitors does not prevent hyponatremia. However, prospective randomized data suggest their efficacy at a higher dosage in overt SIAD.