Metformin has been shown to modulate meta-inflammation, an important pathogenesis in knee osteoarthritis (OA). The study aimed to test the association between regular metformin use with total knee replacement (TKR) in patients with diabetes. This is a retrospective study with electronic records retrieved in Hong Kong public primary care. Patients with diabetes aged ≥ 45 who visited during 2007 to 2010, were followed up for a four-year period from 2011 to 2014 to determine the incidence of TKR. Propensity score matching based on age, sex, co-medications and chronic conditions was conducted to adjust for confounding. Cox regression was implemented to examine the association between metformin use and TKR. In total, 196,930 patients were eligible and 93,330 regular metformin users (defined as ≥ 4 prescriptions over the previous year) and non-users were matched. Among 46,665 regular users, 184 TKRs were conducted, 17.1% fewer than that among non-users. Cox regression showed that regular metformin users had a 19%-lower hazard of TKR [hazard ratio (HR) = 0.81, 95% confidence interval: 0.67 to 0.98, P = 0.033], with a dose-response relationship. Findings suggest a potential protective effect of metformin on knee OA progression and later TKR incidence among diabetic patients.
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