Metformin treatment for patients with hand osteoarthritis: protocol for the multicentre, randomised, placebo-controlled METRO trial.

introductionHand osteoarthritis (OA) is a prevalent joint disorder with limited treatment options. Accumulating evidence suggests that the antidiabetic drug metformin has beneficial effects on knee OA and may likewise be beneficial for hand OA. The objective of this randomised, double-blinded, placebo-controlled trial is to investigate the effect of metformin 1000 mg two times a day, or maximum tolerated dose, compared with placebo on reducing finger joint pain after 16 weeks of treatment. METHODS AND ANALYSIS: The participants will be enrolled from the OA clinic at the Parker Institute at Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark and from the Department of Rheumatology, Hospitalsenhed Midt, Silkeborg, Denmark. 150 participants with painful hand OA according to the American College of Rheumatology criteria will be randomly allocated in a 1:1 ratio to receive either metformin or a matching placebo for 16 weeks. The initial dose of 500 mg of metformin or placebo once daily is increased by 500 mg every week until the target dose of 1000 mg two times a day, or the maximum tolerated dose, is reached. The participants will have clinical visits every 4 weeks, except the week 12 visit, which is by telephone. The primary endpoint is the between-group difference in least squares means for the change in the Visual Analogue Scale (VAS) finger joint pain scores between the metformin and placebo groups at 16 weeks. The main analysis will be conducted on the intention-to-treat population, comprising all participants assessed and randomly assigned at baseline. Least squares means and the differences between them, along with their respective 95% CIs, will be derived from a mixed-effects model for repeated measurements (outcomes collected at baseline and at weeks 4, 8, 12 and 16). Adverse events will be registered systematically. ETHICS AND DISSEMINATION: Approval has been obtained from the European Medicines Agency (EudraCT: 2023-509181-38-00), which also includes approval from the local health research ethics committee. Written informed consent will be obtained from all participants. Study findings will be published in international peer-reviewed journals and will be presented in relevant media and at international scientific conferences. TRIAL REGISTRATION NUMBER: EudraCT, 2023-509181-38-00; ClinicalTrials.gov, NCT06367283.