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Sodium-Glucose Cotransporter-2 Inhibitors in Depression
David T Liebers1, Wataru Ebina, Dan V Iosifescu
1From Department of Psychiatry, New York University Grossman School of Medicine (Drs. Liebers and Iosifescu); Division of Hematology and Medical Oncology, New York University Grossman School of Medicine (Dr. Ebina); Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY (Dr. Iosifescu).
Abstract:
Novel treatment strategies that refract existing treatment algorithms for depressive disorders are being sought. Abnormal brain bioenergetic metabolism may represent an alternative, therapeutically targetable neurobiological basis for depression. A growing body of research points to endogenous ketones as candidate neuroprotective metabolites with the potential to enhance brain bioenergetics and improve mood. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally approved for the treatment of diabetes, induce ketogenesis and are associated with mood improvement in population-based studies. In this column, we highlight the rationale for the hypothesis that ketogenesis induced by SGLT2 inhibitors may be an effective treatment for depressive disorders.
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Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:

