Metformin Treatment on Cognitive Impairment of Schizophrenia Co-morbid Metabolic Syndrome

Summary

In this study, the investigators will investigate the impact and the related mechanism of metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic syndrome. Patients will be randomized to the metformin group or non-metformin control group (40 patients per arm) for 24 weeks. Clinical assessment will be done at screen/baseline, 4 weeks, 12 weeks, and 24 weeks. The specific aims are to compare the metformin group versus controls on 1) clinical core symptoms; 2) cognition. Biological samples also will be collected, and stored to research related mechanisms.

Timeline

Start

2017-08-28

Primary completion

2023-12-31

Completion

2023-12-31

Publications

• Background Lindenmayer JP, Khan A, Kaushik S, Thanju A, Praveen R, Hoffman L, Cherath L, Valdez G, Wance D. Relationship between metabolic syndrome and cognition in patients with schizophrenia. Schizophr Res. 2012 Dec;142(1-3):171-6. doi: 10.1016/j.schres.2012.09.019. Epub 2012 Oct 26.
• Background Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med. 2017 Apr;47(6):1030-1040. doi: 10.1017/S0033291716003366. Epub 2016 Dec 29.
• Background Ying MA, Maruschak N, Mansur R, Carvalho AF, Cha DS, McIntyre RS. Metformin: repurposing opportunities for cognitive and mood dysfunction. CNS Neurol Disord Drug Targets. 2014;13(10):1836-45. doi: 10.2174/1871527313666141130205514.
• Cai J, Xiao J, Long Y, Cao T, Lin C, Hei G, Wang W, Kang D, Huang J, Shao T, Cai H, Wu R. Metformin-improved cognitive impairment in patients with schizophrenia is correlated with activation of tricarboxylic acid cycle and restored functional connectivity of hippocampus. BMC Med. 2025 Jul 1;23(1):349. doi: 10.1186/s12916-025-04218-4.
• Shao T, Huang J, Zhao Y, Wang W, Tian X, Hei G, Kang D, Gao Y, Liu F, Zhao J, Liu B, Yuan TF, Wu R. Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex. Transl Psychiatry. 2023 Oct 11;13(1):315. doi: 10.1038/s41398-023-02616-x.

Drugs

Indications