Safety and efficacy of metformin for the treatment of pain: protocol for a systematic review.

Abstract

Pain remains difficult to manage due to limited efficacy and adverse effects of many existing analgesics, highlighting the need for safer non-opioid treatment strategies. Metformin is a widely prescribed oral antihyperglycaemic agent with emerging preclinical and early clinical evidence suggesting potential analgesic effects. Proposed mechanisms include activation of AMP-activated protein kinase with downstream inhibition of mammalian target of rapamycin and mitogen-activated protein kinase signalling pathways implicated in nociceptive sensitisation and chronic pain. This protocol describes a systematic review to evaluate the efficacy and safety of metformin for the treatment or prevention of pain in an adult population. This systematic review will include randomised, double-blind, placebo or active-controlled trials evaluating orally administered metformin for the treatment or prevention of acute or chronic pain in adult human participants. Searches will be conducted in MEDLINE (Ovid MEDLINE ALL), EMBASE and the Cochrane Central Register of Controlled Trials from inception alongside ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and reference list screening. Two reviewers will independently screen studies, extract data and assess risk of bias using the Cochrane Risk of Bias 2.0 tool. Outcomes will include pain intensity, pain relief, responder outcomes, functional interference, analgesic use and adverse events. Where appropriate, random-effects meta-analyses will be performed. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Ethics approval is not required as this study will synthesise published data. Findings will be disseminated through peer-reviewed publication and presentation in scientific conferences. CRD420261296816.