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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.