IMPACT OF METFORMIN AND SERRATIOPEPTIDASE IN OBESE PATIENTS WITH KNEE OSTEOARTHRITIS
Keywords:Knee osteoarthritis, Inflammatory parameters, Metformin, Serratiopeptidase
Objective: Knee osteoarthritis is a common disabling chronic disease globally. Many pharmacological agents have been used efficiently in treatment of knee osteoarthritis. This study aims to evaluate metformin and serratiopeptidase together in treatment and stop of osteoarthritis progression by different mechanisms.
Methods: Present study was a randomized clinical trial study conducted in Al-Kindi teaching hospital through the period from 1st January to 30th of May, 2017 on two groups of 80 osteoarthritis patients (group I; treated with metformin 850 mg oral tablets) and (group II; treated with metformin 850 mg oral tablets and serratiopeptidase 20 mg oral tablets). Parameters of two groups were compared with those of 40 normal healthy controls.
Results: Patients in group II showed a highly significant reduction in pain scores post-treatment (p<0.001). Tumor necrosis factor alpha (TNF-Î±), interleukin 1 beta (IL-1ÃŸ) and interleukin 8 (IL-8) levels were significantly lowered among patients in group II treatment (p<0.001). Lower inflammatory parameters levels were observed among healthy controls and the parameters levels of group II patients were lower than those of group I patients.
Conclusion: Metformin and serratiopeptidase regimen was efficient and safe in the treatment of knee osteoarthritis.
Cross M, Smith E, Hoy D, Nolte S, Akcerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Annals Rheumatic Diseases; 2014. Available from: https:// www.google.iq/url?sa=tandrct=jandq=andesrc=sandsource=webandcd. [Last accessed on 02 Jul 2017]
Pritzker K. Pathology of osteoarthritis. In: Osteoarthritis. 2nd edition. Brandt K, Doherty M, Lohmander LS. eds. Oxford University Press: Oxford; 2003. p. 248-58.
Anandacoomarasamy A, Caterson I, Sambrook P, Fransen M, March L. The impact of obesity on the musculoskeletal system. Int J Obes (Lond) 2008;32:211â€“22.
Szoeke C, Dennerstein L, Guthrie J, Clark M, Cicuttini F. The relationship between prospectively assessed body weight and physical activity and prevalence of radiological knee osteoarthritis in postmenopausal women. J Rheumatol 2006;33:1835â€“40.
Runhaar J, Koes BW, Clockaerts S, Bierma-Zeinstra SM. A systematic review on the changed biomechanics of lower extremities in obese individuals: a possible role in the development of osteoarthritis. Obes Rev 2011;12:1071â€“82.
Brooks PM. Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications. Curr Opin Rheumatol 2002;14:573â€“7.
Velasquez MT, Katz JD. Osteoarthritis: another component of metabolic syndrome? Metab Syndr Relat Disord 2010;8:295â€“305.
Arya RK, Jain V. Osteoarthritis of the knee joint: an overview. JIACM 2013;14:154-62.
Richette PJ, Pointou C, Garnero P. Beneficial effects of massive weight loss on symptoms, joint biomarkers and systemic inflammation in obese patients with knee OA. Ann Rheum Dis 2011;70:139-44.
Gudbergsen H, Boesen M, Lohmander LS, Christensen R, Henriksen M, Bartels EM, et al. Weight loss is effective for symptomatic relief in obese subjects with knee osteoarthritis independently of joint damage severity assessed by high-field MRI and radiography. Osteoarthritis Cartilage 2012;20:495â€“502.
Srinivasan A, Venkatachlam T, Thamotharan G, Sekar G. Assessment of the efficacy of aceclofenac versus tramadol in osteoarthritis patients. Int J Appl Pharm Biol Res 2016;1:40-6.
Mason L, Moore RA, Edwards JE. Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis. BMC Musculoskelet Disord 2004;5:28.
Clegg D, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-8.
Bartels EM, Bliddal H, Schondorff PK, Altman RD, Zhang W, Christensen R. Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a metaanalysis of randomized placebo-controlled trials. Osteoarthritis Cartilage 2010;18:289-96.
Kon E, Mandelbaum B, Buda R, Filardo G, Delcoqliano M, Timoncini A, et al. Platelet-rich plasma intraarticular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy 2011;27:1490-501.
Barnett LA, Jordan KP, Edwards JJ, van der Windt DA. Does metformin protect against osteoarthritis? An electronic health record cohort study. Prim Health Care Res Dev 2017;18:623-8.
Bhagat S, Agarwal M, Roy V. Serratiopeptidase: a systematic review of the existing evidence. Int J Surg 2013;11:209-17.
Seifarth C, Schehler B, Schneider H. Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes 2013;121:27-31.
Yuan H, Li L, Zheng W, Wan J, Ge P, Li H, et al. Antidiabetic drug metformin alleviates endotoxin-induced fulminant liver injury in mice. Int Immunopharmacol 2012;12:682â€“8.
Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013;21:16-21.
Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes. A randomized, double-blind study versus diclofenac. Clin Drug Invest 2000;19:15-23.
Valayannopoulos V, Brassier A, Chabli A, Caillaud C, Lemoine M, Odent T, et al. Enzyme replacement therapy for lysosomal storage disorders. Arch Pediatr 2011;18:1119â€“23.
Verma MK, Pulicherla KK. Enzyme promiscuity in Earthworm serine protease-Substrate versatility and therapeutic potential. Amino Acids 2016;48:941â€“8.
Malshe PC. Orally administered serratiopeptidase: can it work? J Assoc Physicians India 1998;46:492.
Iraqi ministry of health, Directorate of public health and primary health care and Iraqi ministry of planning and development cooperation, central organization for statistics and information in collaboration with WHO. Chronic none-communicable diseases risk factors survey; 2006. Available from: http://www.fineprint.com [Last accessed on 02 Jul 2017]
Leong DJ, Choudhury M, Hirsh DM, Hardin JA, Cobelli NJ, Sun HB. Nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis. Int J Mol Sci 2013;14:23063-85.
Ortiz MI. Synergistic interaction between metformin and sulfonylureas on diclofenac-induced antinociception measured using the formalin test in rats. Pain Research and Management. Pain Res Manag 2013;18:253-8.
Mohammed MM, Al-Shamma KJ, Jassim NA. 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. Iraqi J Pharm Sci 2014;23:13-23.
Cheng AY, Fantus IG. Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ 2005;172:213â€“26.
Andrews M, Soto N, Arredondo M. Effect of metformin on the expression of tumor necrosis factor-Î±, Toll-like receptors 2/4 and C reactive protein in obese type-2 diabetic patients. Rev Med Chile 2012;140:1377-82.
Cortizo AM, Sedlinsky C, McCarthy AD, Blanco A, Schurman L. Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture. Eur J Pharmacol 2006;536(1-2):38â€“46.
Chen D, Xia D, Pan Z, Xu D, Zhou Y, Wu Y, et al. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. Cell Death Dis 2016;7:e2441.
Levri KM, Slaymaker E, Last A, Ference J, D'Amico F, Wilson SA. Metformin as a treatment for overweight and obese adults: a systematic review. Ann Fam Med 2005;3:457-61.
Imbimbo BP. The potential role of non-steroidal anti-inï¬‚ammatory drugs in treating Alzheimerâ€™s disease. Expert Opin Investig Drugs 2004;13:1469â€“81.
Jadav SP, Patel NH, Shah TG, Gajera MV, Trivedi HR, Shah BK. Comparison of antiinï¬‚ammatory activity of serratiopeptidase and diclofenac in albino rats. J Pharmacol Pharmacother 2010;1:116-7.
Ingle P, Lathi V, Patil P, Surana S, Shirath N. Evaluation of symptomatic efficacy and safety of diclofenac versus etrocoxib in combination with serratiopeptidase in knee osteoarthritis. Pharmagene 2014;1:10-4.
Tiwari M. The role of serratiopeptidase in the resolution of inflammation. Asian J Pharm Sci 2017;12:209â€“15.
Chappi DM, Suresh KV, Patil MR, Desai R, Tauro DP, Bharani KNSS, et al. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. J Clin Exp Dent 2015;7:e197-202.
Aiswarya S, Parvathy S, Aneesh TP, Viswanad V. Design and in vitro characterization of metformin loaded resealed erythrocytes. Asian J Pharm Clin Res 2017;10:231-8.