Evaluation of the Clinical use of Metformin or Pioglitazone in Combination with Meloxicam in Patients with Knee Osteoarthritis; using Knee Injury and Osteoarthritis outcome Score

Mohammed, Mohammed M.; Al-Shamma, Kassim J.; Jassim, Nizar Abdulateef

doi:10.31351/vol23iss2pp13-23

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…The results of another clinical trial in OA patients confirm the beneficial effects of metformin such as changes in western Ontario and McMaster universities osteoarthritis index (WOMAC) score and visual analog scale (VAS) knee pain with a maximum dose of 2 g/day for 24 months [ 71 ]. In another study, the results showed that metformin (1000 mg/day for 12 weeks) in combination with meloxicam (15 mg/day) significantly improved KOOS components compared to the setting that meloxicam was used alone in OA patients [ 72 ]. Recently, some studies have reported the therapeutic influence of metformin on reducing cartilage degeneration and joint pain in animal models and cohort studies [ 73 – 76 ].…”

Section: Discussionmentioning

confidence: 99%

Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA

et al. 2023

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Objective This study aimed to evaluate the effectiveness of metformin versus placebo in overweight patients with knee osteoarthritis (OA). In addition, to assess the effects of inflammatory mediators and apoptotic proteins in the pathogenesis of OA, the genetic polymorphisms of two genes, one related to apoptosis (rs2279115 of Bcl-2) and the other related to inflammation (rs2277680 of CXCL-16), were investigated. Methods In this double-blind placebo-controlled clinical trial, patients were randomly divided to two groups, one group receiving metformin (n = 44) and the other one receiving an identical inert placebo (n = 44) for 4 consecutive months (starting dose 0.5 g/day for the first week, increase to 1 g/day for the second week, and further increase to 1.5 g/day for the remaining period). Another group of healthy individuals (n = 92) with no history and diagnosis of OA were included in this study in order to evaluate the role of genetics in OA. The outcome of treatment regimen was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. The frequency of variants of rs2277680 (A181V) and rs2279115 (938C>A) were determined in extracted DNAs using PCR-RFLP method. Results Our results indicated an increase in scores of pain (P ≤ 0.0001), activity of daily living (ADL) (P ≤ 0.0001), sport and recreation (Sport/Rec) (P ≤ 0.0001), and quality of life (QOL) (P = 0.003) and total scores of the KOOS questionnaire in the metformin group compared to the placebo group. Susceptibility to OA was associated with age, gender, family history, CC genotype of 938C>A (Pa = 0.001; OR = 5.2; 95% CI = 2.0–13.7), and GG+GA genotypes of A181V (Pa = 0.04; OR = 2.1; 95% CI = 1.1–10.5). The C allele of 938C>A (Pa = 0.04; OR = 2.2; 95% CI = 1.1–9.8) and G allele of A181V (Pa = 0.02; OR = 2.2; 95% CI = 1.1–4.8) were also associated with OA. Conclusion Our findings support the possible beneficial effects of metformin on improving pain, ADL, Sport/Rec, and QOL in OA patients. Our findings support the association between the CC genotype of Bcl-2 and GG+GA genotypes of CXCL-16 and OA.

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Section: Discussionmentioning

confidence: 99%

Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA

et al. 2023

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“…In preclinical studies, in addition to chondroprotective and anti-inflammatory effects, metformin was shown to be able to improve pain, such that rats or mice treated with metformin showed increased paw withdraw latency indicative of reduction in pain 13 15 16 35. In human studies, a randomised, double-blind trial showed that the combination of metformin with meloxicam improved knee pain by at least 50% more than meloxicam alone 36. Additionally, one of the metformin’s pleiotropic effects is mild weight loss (~2.5%),37 which is important when tackling the slow insidious weight creep from early to middle adulthood,38–40 particularly when obesity is a well-known risk factor for OA, and for more symptomatic and more progressive knee OA.…”

Section: Discussionmentioning

confidence: 99%

Metformin for knee osteoarthritis with obesity: study protocol for a randomised, double-blind, placebo-controlled trial

Lim,

Wang,

Urquhart

et al. 2023

BMJ Open

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IntroductionOver half of the populations with knee osteoarthritis (OA) have obesity. These individuals have many other shared metabolic risk factors. Metformin is a safe, inexpensive, well-tolerated drug that has pleiotropic effects, including structural protection, anti-inflammatory and analgesic effects in OA, specifically the knee. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether metformin reduces knee pain over 6 months in individuals with symptomatic knee OA who are overweight or obese.Methods and analysisOne hundred and two participants with symptomatic knee OA and overweight or obesity will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either metformin 2 g or identical placebo daily for 6 months. The primary outcome is reduction of knee pain [assessed by 100 mm Visual Analogue Scale (VAS)] at 6 months. The secondary outcomes are OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) responder criteria [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and participant’s global assessment (VAS)] at 6 months; change in knee pain, stiffness, function using WOMAC at 6 months and quality of life at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups.Ethics and disseminationEthics approval has been obtained from the Alfred Hospital Ethics Committee (708/20) and Monash University Human Research Ethics Committee (28498). Written informed consent will be obtained from all the participants. The findings will be disseminated through peer-review publications and conference presentations.Trial registration numberACTRN12621000710820 .

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“…In a clinical trial in patients with symptomatic, radiologically confirmed knee OA, a greater reduction in serum levels of IL-1β, IL-8, and TNF-α was found in patients treated with metformin and meloxicam compared to those receiving meloxicam alone over a 12-week period [ 71 ]. In patients with OA and type II diabetes mellitus, the combined administration of a COX-2 inhibitor and metformin resulted in a reduced incidence of joint replacement compared with patients receiving a COX-2 inhibitor alone during a 10-year period of follow-up [ 72 ].…”

Section: Pleiotropic Effects Of Metformin In Osteoarthritismentioning

confidence: 99%

Pleiotropic Effects of Metformin in Osteoarthritis

Lambova

2023

Life

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The involvement of the knee joint is the most common localization of the pathological process in osteoarthritis (OA), which is associated with obesity in over 50% of the patients and is mediated by mechanical, inflammatory, and metabolic mechanisms. Obesity and the associated conditions (hyperglycemia, dyslipidemia, and hypertension) have been found to be risk factors for the development of knee OA, which has led to the emerging concept of the existence of a distinct phenotype, i.e., metabolic knee OA. Combined assessment of markers derived from dysfunctional adipose tissue, markers of bone and cartilage metabolism, as well as high-sensitivity inflammatory markers and imaging, might reveal prognostic signs for metabolic knee OA. Interestingly, it has been suggested that drugs used for the treatment of other components of the metabolic syndrome may also affect the clinical course and retard the progression of metabolic-associated knee OA. In this regard, significant amounts of new data are accumulating about the role of metformin—a drug, commonly used in clinical practice with suggested multiple pleiotropic effects. The aim of the current review is to analyze the current views about the potential pleiotropic effects of metformin in OA. Upon the analysis of the different effects of metformin, major mechanisms that might be involved in OA are the influence of inflammation, oxidative stress, autophagy, adipokine levels, and microbiome modulation. There is an increasing amount of evidence from in vitro studies, animal models, and clinical trials that metformin can slow OA progression by modulating inflammatory and metabolic factors that are summarized in the current up-to-date review. Considering the contemporary concept about the existence of metabolic type knee OA, in which the accompanying obesity and systemic low-grade inflammation are suggested to influence disease course, metformin could be considered as a useful and safe component of the personalized therapeutic approach in knee OA patients with accompanying type II diabetes or obesity.

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Evaluation of the Clinical use of Metformin or Pioglitazone in Combination with Meloxicam in Patients with Knee Osteoarthritis; using Knee Injury and Osteoarthritis outcome Score

Cited by 11 publications

References 30 publications

Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA

Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA

Metformin for knee osteoarthritis with obesity: study protocol for a randomised, double-blind, placebo-controlled trial

Pleiotropic Effects of Metformin in Osteoarthritis

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