Metformin Repurposing in Neurological Disorders: A Clinical Trial Landscape

Neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis (MS) involve progressive nerve cell loss and current treatments mainly provide symptomatic relief without stopping disease progression. Drug repurposing offers a promising approach to address this gap. Metformin, a widely used oral anti-diabetic drug, is being studied in central nervous system (CNS) disorders due to its multiple effects, including activating the adenosine monophosphate-activated protein kinase (AMPK) pathway, supporting neuroprotection and promoting remyelination.

To systematically analyse the current clinical trial landscape of metformin repurposing in CNS disorders.

Data were collected exclusively from ClinicalTrials.gov. The search focused on neurological, neurodegenerative and neurodevelopmental conditions while excluding trials mainly targeting type 2 diabetes or cancer. After screening, 23 clinical studies were selected. Extracted data emphasised disease types, therapeutic goals and measurable neurobiological and functional outcomes.

Research on metformin in CNS disorders is active, with over two-thirds of trials being completed (N = 7, 30.4%) or recruiting (N = 9). Most studied conditions include MS (N = 5), schizophrenia/psychosis (N = 4) and fragile X syndrome (FXS) (N = 4), highlighting interest in neurodevelopmental and demyelinating repair. Trials use functional outcomes such as the Timed 25-Foot Walk Test (T25FWT) and the MATRICS Consensus Cognitive Battery (MCCB), along with advanced biomarkers such as diffusion tensor imaging (DTI) for white matter integrity and molecular markers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).

This analysis shows growing interest in repurposing metformin as a potential disease-modifying therapy for CNS disorders, with a focus on neurorepair and biomarker-based assessment. Larger, well-designed randomised controlled trials are still needed to confirm efficacy in humans.