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

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Summary

Introduction

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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