Metformin as a Potential Disease-Modifying Drug in Osteoarthritis: A Systematic Review of Pre-Clinical and Human Studies

Lim, Yujin; Wang, Y.; Estee, Mahnuma Mahfuz; Abidi, J.; Kumar, Maushmi Udaya; Hussain, Sultana Monira; Wluka, A.; Little, C.B.; Cicuttini, F.

doi:10.1016/j.joca.2022.02.596

Cited by 1 publication

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“…Consistent with previous studies, our study found solid evidence to support a significant association between MET use and TKA occurrence and the degree of knee pain before and after the adjustment of clinically important covariates. Moreover, our study supplemented the analyses of accumulative and dose-dependent effects of MET use with the reduced risk of TKA as well as the degree of knee pain, which, to some extent, fills the gap in previous studies [ 18 ].…”

Section: Discussionmentioning

confidence: 98%

“…Furthermore, previous studies have indicated that MET may attenuate neuropathic pain, and this effect may be through the activation of opioidergic mechanisms or regulation of pain mediators via the autophagy-lysosomal pathway [ 26 , 27 , 28 ]. In terms of the molecular pathways of MET effects on OA, most previous studies described that AMPK activation can modulate the chondroprotective, immunomodulatory, and analgesic effects of MET [ 18 ]. In addition, SIRT3/PINK1/Parkin activation and the downregulation of the mTORC1 pathway were also the potential molecular pathways of MET effects on OA [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…In terms of the molecular pathways of MET effects on OA, most previous studies described that AMPK activation can modulate the chondroprotective, immunomodulatory, and analgesic effects of MET [ 18 ]. In addition, SIRT3/PINK1/Parkin activation and the downregulation of the mTORC1 pathway were also the potential molecular pathways of MET effects on OA [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…A systematic review of pre-clinical and human studies of the effects of MET on OA concluded that MET exerted favorable effects on chondroprotection, immunomodulation, and pain reduction in knee OA. Notably, there was only one study detecting the association between MET use and the severity of knee pain, which is considered the most important symptom of OA [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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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

Chen

Ruan

Zeng

et al. 2022

JCM

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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.

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Section: Discussionmentioning

confidence: 98%