Abstract
ObjectiveTo examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis.MethodsThis study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m2). 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 4 years. Total knee replacement over 6 years 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 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (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.
Highlights
Osteoarthritis (OA) is one of the leading causes of global disability, resulting in over 12.8 million years lived with disability in 2015, an increase of 34.8% since 2005 [1]
Among 818 participants included in the current study, 56 (6.8%) were metformin users
There were no significant differences in terms of baseline age, gender, Body mass index (BMI), diabetes, metformin use, or weight change over 4 years between participants with and without knee cartilage volume assessed at 4-year follow-up
Summary
Osteoarthritis (OA) is one of the leading causes of global disability, resulting in over 12.8 million years lived with disability in 2015, an increase of 34.8% since 2005 [1]. Drugs targeting obesity and its associated inflammatory and metabolic abnormalities have the potential to slow the progression of knee OA. In patients with OA and type 2 diabetes, a combination of cyclooxygenase (COX)-2 inhibitors and metformin reduced the rate of joint replacement over 10 years compared with COX-2 inhibitors alone [11]. Given the biological effects of metformin, knee OA patients with the obese phenotype represent the subgroup most likely to benefit from metformin which might be a potential disease-modifying agent in knee OA. The aim of our study was to determine whether metformin use was associated with a reduction in loss of knee cartilage volume over 4 years and risk of total knee replacement over 6 years in obese individuals with knee OA. It was hypothesised that metformin use would be associated with a reduced rate of cartilage volume loss and reduced risk of total knee replacement
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