The efficacy of metformin for pain, function, and quality of life in knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND

Knee osteoarthritis (KOA) is a leading cause of disability worldwide; however current therapies offer only symptomatic relief. Metformin, a widely used antidiabetic agent, has been demonstrated to have anti-inflammatory and chondroprotective effects in preclinical models, suggesting its KOA modifying properties.

METHODS

We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effects of metformin in patients with KOA. A comprehensive search of PubMed, Embase, and Cochrane Library was performed up to May 2025. Two reviewers independently screened studies and extracted data. Statistical analyses were conducted using a random-effects model to account for between-study heterogeneity. Subgroup analyses based on formulation, treatment duration, and nonsteroidal anti-inflammatory drugs (NSAIDs) co-administration were also performed.

RESULTS

Five studies (n = 337) were included. Metformin significantly reduced pain scores (standardized mean difference [SMD] = -1.295; 95 % confidence interval [CI]: -2.063 to -0.526) and stiffness (SMD = -0.746; 95 % CI: -1.385 to -0.107), improved physical function (SMD = -2.042; 95 % CI: -3.372 to -0.712), and health-related quality of life (SMD = -1.505; 95 % CI: -2.896 to -0.115). Effects were consistent regardless of oral or topical metformin use, treatment duration, and NSAID use, although the benefits were greater when metformin was combined with NSAIDs.

CONCLUSION

While metformin demonstrated consistent benefits in pain and functional outcomes, these findings should be interpreted as symptomatic and adjunctive effects rather than definitive disease modification. Future trials incorporating structural endpoints are needed to confirm disease-modifying potential.