Metformin's therapeutic potential in spinal cord injury: a systematic review and meta-analysis on locomotor recovery, neuropathic pain alleviation, and modulation of secondary injury mechanisms
Abstract
OBJECTIVE: To evaluate metformin's efficacy in locomotion recovery, alleviating neuropathic pain, and modulating underlying molecular mechanisms in Spinal Cord Injury (SCI) rodent models through a systematic review and meta-analysis.
METHODS: We conducted a comprehensive literature search across Medline, Embase, Scopus, and Web of Science from inception to May 2024. We included studies that utilized rodent models of traumatic SCI treated with metformin versus untreated controls. Data on locomotor recovery, neuropathic pain, and molecular mechanisms related to secondary injury were extracted. Standardized mean differences (SMDs) were synthesized as the pooled effect sizes.
RESULTS: Twenty-three studies comprising 1,567 animals met the inclusion criteria. Metformin significantly enhanced locomotor function (SMD = 2.23, 95% CI: 1.74, 2.73, p < 0.001) and improved both mechanical allodynia (SMD = 1.18; 95% CI, 0.35 to 2.00; p = 0.005) and thermal hyperalgesia (SMD = 2.40; 95% CI, 1.65 to 3.16; p < 0.001). It reduces inflammation, oxidative stress, microglial activation, and astrogliosis and promotes myelination and autophagy flux via activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. This resulted in decreased apoptosis and lesion size and increased tissue preservation and neuronal survival. Subgroup analyses indicated greater locomotor improvements when metformin was administered in the acute (< 3 days of injury) phase of the injury…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
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.