Association between Metformin Use and Risk of Total Knee Arthroplasty and Degree of Knee Pain in Knee Osteoarthritis Patients with Diabetes and/or Obesity: A Retrospective Study

Abstract

Objectives: We aimed to examine whether metformin (MET) use is associated with a reduced risk of total knee arthroplasty (TKA) and low severity of knee pain in patients with knee osteoarthritis (OA) and diabetes and/or obesity. Methods: Participants diagnosed with knee OA and diabetes and/or obesity from June 2000 to July 2019 were selected from the information system of a local hospital. Regular MET users were defined as those with recorded prescriptions of MET or self-reported regular MET use for at least 6 months. TKA information was extracted from patients’ surgical records. Knee pain was assessed using the numeric rating scale. Log-binomial regression, linear regression, and propensity score weighting (PSW) were performed for statistical analyses. Results: A total of 862 participants were included in the analyses. After excluding missing data, there were 346 MET non-users and 362 MET users. MET use was significantly associated with a reduced risk of TKA (prevalence ratio: 0.26, 95% CI: 0.15 to 0.45, p < 0.001), after adjustment for age, gender, body mass index, various analgesics, and insurance status. MET use was significantly associated with a reduced degree of knee pain after being adjusted for the above covariates (β: −0.48, 95% CI: −0.91 to −0.05, p = 0.029). There was a significantly accumulative effect of MET use on the reduced risk of TKA. Conclusion: MET can be a potential therapeutic option for OA. Further clinical trials are needed to determine if MET can reduce the risk of TKA and the severity of knee pain in metabolic-associated OA patients.

Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea

“…A population-based cohort study reported a reduced incidence of total knee arthroplasty in individuals with preexisting OA and diabetes who had received a combination of metformin and a cyclooxygenase-2 inhibitor compared with a cyclooxygenase-2 inhibitor alone . Additional cohort studies have found that individuals with diabetes treated with metformin had a significantly reduced risk of total knee arthroplasty . One cohort study found no association between metformin use and incidence of developing OA; however, a systematic review of 10 preclinical and 5 human studies of OA concluded that metformin had chondroprotective, immunomodulatory, and analgesic associations .…”

“…7 Emerging evidence suggests that metformin may be useful for the treatment or prevention of OA. [8][9][10][11][12][13][14][15] Preclinical studies suggest that metformin has disease-modifying properties in OA models in mice, rats, and macaque monkeys. 9,10 Observational studies in humans have also largely supported the use of metformin associated with preventing the development of OA or the need for joint replacement.…”

“…Emerging evidence suggests that metformin may be useful for the treatment or prevention of OA . Preclinical studies suggest that metformin has disease-modifying properties in OA models in mice, rats, and macaque monkeys .…”

“… 9 , 10 Observational studies in humans have also largely supported the use of metformin associated with preventing the development of OA or the need for joint replacement. 8 , 13 , 14 , 15 However, these studies have predominately focused on progression of preexisting OA (as opposed to the development of incident OA); many have not accounted for concomitant antidiabetic medication use, thus failing to fully isolate the effects of metformin; and some have suffered from immortal time bias related to the comparison of metformin users and nonusers (as opposed to an active treatment control arm).…”

Metformin as a Promising Anti-Aging Agent in the Treatment of Osteoarthritis

“…The authors hypothesized this could be due to the synergistic anti-inflammatory effect of the combination [37]. Real-world data from retrospective registry-based studies showed that metformin intake was linked to a reduction in knee pain in OA patients [38] and lower risk for total knee arthroplasty (TKA) with accumulative effectiveness over time in those with T2DM or obesity [38,39].On contrary, Barnett et al found no association between exposure to metformin and OA onset in patients with T2DM [40].…”