Sodium-Glucose Cotransporter-2 Inhibitors in Mood Disorders: A Narrative Review of Mechanisms, Evidence, and Challenges
Abstract
Mood disorders, including major depressive disorder and bipolar disorder, are frequently comorbid with metabolic syndrome, contributing to greater illness severity and poorer outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), a novel class of anti-diabetic agents, not only improve glycemic control but have also shown potential neuroprotective and cognitive benefits. This narrative review summarizes preclinical and clinical evidence on the application of SGLT-2i in mood disorders, with emphasis on their multifaceted mechanisms, including metabolic modulation, anti-inflammatory and antioxidant effects, mitochondrial protection, autophagy regulation, and enhancement of neurotrophic signaling. But it is also notable that current evidence remains limited and heterogeneous. Most clinical data derive from observational studies in diabetic populations and evidence supporting therapeutic effects in patients with established mood disorders is still preliminary. Other important limitations include the scarcity of disorder-specific randomized controlled trials, uncertainty regarding long-term safety in psychiatric populations, and potential interactions with psychotropic medications. Collectively, SGLT-2i may represent a mechanistically relevant and clinically exploratory approach at the interface of metabolic and psychiatric disorders, though further high-quality studies are required to establish their efficacy and safety in mood disorder populations.
Read the paper
Related studies
- The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity
- Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism
- Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model
- Modulating Sirtuin Biology and Nicotinamide Adenine Diphosphate Metabolism in Cardiovascular Disease—From Bench to Bedside
- Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis
- Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.