SGLT2 Inhibitors Associated With Improved Kidney Function in Lithium‐Treated Patients With Mood Disorders: A Real‐World Historical Cohort Study

INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed for type 2 diabetes, have shown promise in improving renal outcomes in patients with and without diabetes. However, their effect on lithium-associated kidney dysfunction remains unknown. METHODS: This historical cohort study included patients from Mayo Clinic (2001-2023) with mood disorders who received lithium for ≥ 6 months and later used SGLT2i for ≥ 1 month. Data on SGLT2i use and lithium treatment were extracted from electronic health records. Serum creatinine values were used to calculate estimated glomerular filtration rate (eGFR) trajectories. Linear mixed-effects models with piecewise linear splines were used to estimate eGFR slopes before and after SGLT2i initiation, adjusted for age and sex. RESULTS: per year, reflecting a + 2.13 change (p = 0.025). Sensitivity analyses, including only patients on lithium at SGLT2i initiation (n = 22) or who had > 1 year of SGLT2i use (n = 29) showed similar, though non-significant, changes in slopes. CONCLUSION: SGLT2i treatment was associated with a significant improvement in eGFR trajectory in patients with mood disorders who received long-term lithium therapy. These findings suggest a potential role for SGLT2is in mitigating lithium-associated kidney dysfunction and highlight the need for randomized controlled trials in this population.