Association between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiativea prospective cohort study

ObjectiveTo examine whether metformin use was associated with knee cartilage volume loss over 4years and risk of total knee replacement over 6years in obese individuals with knee osteoarthritis.MethodsThis study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade2) who were obese (body mass index [BMI] 30kg/m(2)). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n=56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n=762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4years. Total knee replacement over 6years was assessed. General linear model and binary logistic regression were used for statistical analyses.ResultsThe rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of -0.86% per annum (95% CI -1.58% to -0.15%, p=0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6years (odds ratio 0.30, 95% CI 0.07-1.30, p=0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes.ConclusionsThese data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.