Association of Metformin Use with Osteoarthritis Incidence, Progression, and Joint Arthroplasty Risk in the Knee and Hip: A Systematic Review and Meta-Analysis.

Abstract

Although hip and knee osteoarthritis (OA) constitutes a major cause of disability globally, disease-modifying therapies do not exist. Preclinical evidence suggests that metformin has disease-modifying potential, but clinical evidence is conflicting. This meta-analysis assessed the effect of metformin on 1) hip/knee OA incidence, 2) radiographic/symptomatic progression, and 3) joint arthroplasty (JA) risk. We systematically searched the PubMed, Web of Science, Embase, and Cochrane Library databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Random-effects meta-analyses and qualitative synthesis were performed for the prespecified outcomes. Evidence from 13 studies enrolling 167,107 cases demonstrated that metformin users had a 33% lower hip/knee OA incidence (pooled risk ratios (RRs) 0.67, 95% confidence intervals (CI) 0.61 to 0.74). Qualitative synthesis indicated reduced magnetic resonance imaging-assessed medial cartilage loss and delayed symptomatic progression with respect to pain, joint function, and quality of life among metformin users. Crucially, metformin was associated with a 43% lower JA risk (pooled RR 0.57, 95% CI: 0.38 to 0.84), with enhanced protection in those who had pre-existing OA versus those who had diabetes/obesity alone (RR 0.37 versus 0.81) and those receiving more than two years versus two years or less of treatment (RR 0.38 versus 0.80). Metformin may reduce hip/knee OA incidence and slow radiographic/symptomatic progression. It significantly reduces the risk of JA, particularly in patients who have pre-existing OA and receive prolonged metformin therapy. These findings support considering metformin in this subgroup while highlighting the need for trials to confirm its efficacy among patients who have diabetes/obesity, but do not have established OA.