SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system
- Transl Neurodegener. 2024 Aug 9;13(1):41. doi: 10.1186/s40035-024-00431-y.
- 1. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
- 2. Huan Kui College of Nanchang University, Nanchang, China.
- 3. The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
- 4. Queen Mary College of Nanchang University, Nanchang, China.
- 5. Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
- 6. Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, China.
- 7. Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. [email protected].
- 8. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China. [email protected].
- # Contributed equally.
The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation.