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AMPK→inflammatory mediator suppression→neuroprotection
Metformin shows protective effects against chemotherapy-induced peripheral neuropathy via AMPK-mediated suppression of inflammatory mediators, though evidence quality is mixed (2/28 supportive, 14 contradicting) likely reflecting heterogeneity between diabetic and chemotherapy-induced etiologies and concerns about B12 deficiency worsening neuropathy. The chemotherapy-induced protection signal is distinct and notable.
“The mechanism of the preventive role of metformin on peripheral neuropathy has been reported to be reduced expression of inflammatory mediators (interleukin-1β, inducible nitric oxide synthase, and nitric oxide) [2], and the anti-oxidative effect occurs via the adenosine monophosphate-activated prot”
— Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats (Diabetes Metab J 2020;44:842-53) (2021)DOI“Metformin ameliorates peripheral neuropathy in diabetic rats by downregulating autophagy via the AMPK pathway.”
— Metformin ameliorates peripheral neuropathy in diabetic rats by downregulating autophagy via the AMPK pathway. (2024)DOI“Metformin decreased the incidence of peripheral neuropathy, bone pain, and arthralgia, although worsened the gastrointestinal adverse events.”
— The impact of metformin use on the outcomes of locally advanced breast cancer patients receiving neoadjuvant chemotherapy: an open-labelled randomized controlled trial. (2022)DOI“These results suggest that 24-week treatment with metformin initiated early in the course of T1DM attenuate the hypersensitivity resulting from axonal degeneration by decreasing systemic inflammation related to hyperglycemia; thus, metformin has therapeutic potential to prevent or delay hyperglycemi”
— The Anti-Diabetic Drug Metformin from the Neuropathy Perspective. (2020)DOI“Addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue (p < 0.05) compared to control arm.”
— The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study. (2023)DOI“The potential application of metformin contains three directions: Firstly, improvement of metabolic factors associated with treatment effects, such as insulin resistance and peripheral neuropathy.”
— Current status and frontier tracking of clinical trials on Metformin for cancer treatment. (2023)DOI