Effect Of Metformin In Obese Knee Osteoarthritis Patients
Keywords:
Anti-Inflammatory, Antioxidant, Antiviral, Gewald Reaction, Hantzsch SynthesisAbstract
Background: Obese knee osteoarthritis (OA) is a debilitating condition driven by mechanical stress and systemic inflammation, with limited treatments that address both symptoms and disease progression. Tramadol is commonly used for pain relief, while metformin, traditionally a diabetes medication, shows promise for its anti-inflammatory and chondroprotective effects. This study compares the efficacy of tramadol alone versus tramadol combined with metformin in managing obese knee OA.
Methods: In a 12-week randomized controlled trial at St. Isabel’s Hospital, Chennai, 50 patients (BMI ≥ 30 kg/m², aged 40–60 years) with obese knee OA were assigned to two groups: Group A (tramadol) and Group B (tramadol + metformin). Outcomes included changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and function, and serum cartilage oligomeric matrix protein (COMP) levels as a biomarker of cartilage degradation. Statistical analysis used paired t-tests to assess significance.
Results: Both groups showed significant improvements in WOMAC scores and COMP levels (p < 0.05). Group B (tramadol + metformin) demonstrated greater reductions in WOMAC total score (60.6 ± 9.03 to 42.6 ± 7.80 vs. 64 ± 9.37 to 51.8 ± 8.98, p = 0.00616), pain (p = 0.030), stiffness (p = 0.0001), and function (p = 0.00679) subscales, and serum COMP levels (14.04 ± 1.87 to 9.8 ± 1.49 vs. Mavericks 14.7 ± 1.82 to 11.9 ± 1.75, p ≤ 0.0001) compared to Group A. No significant BMI changes were observed in either group.
Conclusion: The combination of tramadol and metformin provides superior symptomatic relief and potential chondroprotective benefits compared to tramadol alone in obese knee OA patients. These findings suggest metformin’s potential as an adjunctive therapy, warranting further investigation into its long-term disease-modifying effects
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References
.Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1):16-21.
.Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. The Lancet. 2019;393(10182):1745-1759.
.Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;380(9859):2163-2196. d
Zhang Y, Jordan JM. Epidemiology of Osteoarthritis. Clin Geriatr Med. 2010;26(3):355-369.
Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73(7):1323-1330. doi:10.1136/annrheumdis-2013-204763
6. Zhuo Q, Yang W, Chen J, Wang Y. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol. 2012;8(12):729-737. doi:10.1038/nrrheum.2012.135
Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss reduces knee‐joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum. 2005;52(7):2026-2032.
Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage. 2005;13(9):769-781.
. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. The Lancet. 2011;377(9783):2115-2126.
. Dowsey MM, Choong PFM. Obesity is a Major Risk Factor for Prosthetic Infection after Primary Hip Arthroplasty. Clin Orthop. 2008;466(1):153-158.
. Banks SE. Erosive osteoarthritis: a current review of a clinical challenge. Clin Rheumatol. 2010;29(7):697-706. doi:10.1007/s10067-009-1369-7
. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363-388.
. Gaulton TG, Fleisher LA, Neuman MD. The association between obesity and disability in survivors of joint surgery: analysis of the health and retirement study. Br J Anaesth. 2018;120(1):109-116.
. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578-1589.
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15(12):1833-1840.
. McConnell S, Kolopack P, Davis AM. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum. 2001;45(5):453-461.
. Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS‐PS), Knee Outcome Survey Activities of Daily Living Scale (KOS‐ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS). Arthritis Care Res. 2011;63(S11).
Pham T, Van Der Heijde D, Altman RD, et al. OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage. 2004;12(5):389-399.
. Kumahashi N, Tadenuma T, Kuwata S, Fukuba E, Uchio Y. A longitudinal study of the quantitative evaluation of patella cartilage after total knee replacement by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping at 3.0T: preliminary results. Osteoarthritis Cartilage. 2013;21(1):126-135.
. Posey K, Hecht J. The Role of Cartilage Oligomeric Matrix Protein (COMP) in Skeletal Disease. Curr Drug Targets. 2008;9(10):869-877.
. Peloso PM, Bellamy N, Bensen W, et al. Double-blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee. J Rheumatol. 2000;27(3):764-771.
. Lim YZ, Wang Y, Estee M, et al. Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of pre-clinical and human studies. Osteoarthritis Cartilage. 2022;30(11):1434-1442.
. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578-1589. d
. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1):16-21.
. Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage. 2005;13(9):769-781.
. Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss reduces knee‐joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum. 2005;52(7):2026-2032
. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577-1585
. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363-388.
. Pernicova I, Korbonits M. Metformin—mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014;10(3):143-156. 6
. Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: From Mechanisms of Action to Therapies. Cell Metab. 2014;20(6):953-966.
. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. The Lancet. 2019;393(10182):1745-1759.
. Chen S, Ruan G, Zeng M, Chen T, Cao P, Zhang Y, Li J, Wang X, Li S, Tang SA, Lu S. 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. Journal of Clinical Medicine. 2022 Aug 17;11(16):4796.
Ateia YA, Al-Edanni MS, Al-Qurtas MI. Impact of metformin and serratiopeptidase in obese patients with knee osteoarthritis. Int. J. Pharm. Pharm. Sci. 2018 Feb 1;10(2):37-41.
. Khotib J, Setiawan HU, Nurhan AD, Rahadiansyah E, Ardianto C, Rahmadi M. Analysis of effectiveness and drug related problems of pain reliever for knee osteoarthritis: weighing clinical risk and benefit. Journal of Basic and Clinical Physiology and Pharmacology. 2019 Nov 1;30(6).
Kumar M, Dogra R, Mandal UK. Novel formulation approaches used for the management of osteoarthritis: A recent review. Current Drug Delivery. 2023 Aug 1;20(7):841-56.
Glauser TA, Salinas GD, Roepke NL, Williamson JC, Reese A, Gutierrez G, Abdolrasulnia M. Management of mild-to-moderate osteoarthritis: a study of the primary care perspective. Postgraduate Medicine. 2011 Jan 1;123(1):126-34.
. Xhakaza L, Abrahams-October Z, Pearce B, Masilela CM, Adeniyi OV, Johnson R, Ongole JJ, Benjeddou M. Evaluation of the suitability of 19 pharmacogenomics biomarkers for individualized metformin therapy for type 2 diabetes patients. Drug metabolism and personalized therapy. 2020 Jul 15;35(2):20200111.
Booker SQ, Content VG. Chronic pain, cardiovascular health and related medication use in ageing African Americans with osteoarthritis. Journal of clinical nursing. 2020 Jul;29(13-14):2675-90.
. Seifert R. Drugs easily explained. Springer; 2022 Dec 10.
Aiad AA, El-Haggar SM, El-Barbary AM, El-Afify DR. Metformin as adjuvant therapy in obese knee osteoarthritis patients. Inflammopharmacology. 2024 Aug;32(4):2349-59..
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