EFFECTS OF METFORMIN ON THE WEIGHT OF HEALTHY AND STREPTOZOTOCIN-INDUCED DIABETIC ANIMAL MODEL
AbstractBackground: Metformin was approved by FDA in 1994 for the treatment of type II diabetes mellitus. Due to its interaction with the AMP kinases enzyme system, it showed multiple effects on other organ systems of the body. Despite being the drug of the first choice for type II diabetes it became a popular drug for PCOS and currently, various trials are proving its anticancer effects. Though not approved by FDA it is also responsible for weight loss. The study aims to investigate the effect of metformin on the weight of healthy and streptozotocin-induced diabetic animal models. The study was performed at Animal House, Faculty of Pharmacy Ziauddin University Karachi. Methods: It was a pre-clinical experimental study conducted at Ziauddin University Karachi from August 2019 to December 2019. 36 male Albino rats were divided into 6 groups such with 6 rats in each group. Out of six three were healthy models (i.e., groups 1, 2, and 3) and the remaining three were diabetic models (i.e., Group 4, 5, and 6). Diabetes was induced in groups 4,5 and 6 by using the diabetogenic drug Streptozotocin. In Group 1 and 4, 0.5 ml normal saline was administered, 50 mg/kg (5 mg/100g) metformin diluted in 0.5 ml distilled water was administered in Group 2 and 5 followed by administration of 80 mg/kg (8 mg/100g) metformin diluted in 0.5ml distilled water in Group 3 and 6. the protocol was followed twice a day for 42 days. The weight of all the groups was calculated before and after drug intervention. Results: Metformin-induced weight loss was observed in healthy treated groups at both doses, however, there was no significant difference in weight loss in diabetic treated and untreated groups. Conclusion: Metformin showed weight lowering properties in healthy treated subjects, after induction of diabetes we found weight loss in diabetic untreated and treated groups which suggests that hyperglycemia may cause weight loss but when metformin corrects the hyperglycemic profile it does not lead to an increase in weight.
Bailey CJ. Metformin: historical overview. Diabetologia 2017;60(9):1566–76.
Thomas I, Gregg B. Metformin; a review of its history and future: from lilac to longevity. Pediatr Diabetes 2017;18(1):10–6.
Wang YW, He SJ, Feng X, Cheng J, Luo YT, Tian L, et al. Metformin: a review of its potential indications. Drug Des Devel Ther 2017;11:2421–9.
Wheaton WW, Weinberg SE, Hamanaka RB, Soberanes S, Sullivan LB, Anso E, et al. Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. Elife 2014;3:e02242.
Velazquez E, Mendoza S, Hamer T, Sosa F, Glueck CJM. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994;43(5):647–54.
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017;60(9):1577–85.
Prantner D, Perkins DJ, Vogel SN. AMP-activated kinase (AMPK) promotes innate immunity and antiviral defense through modulation of stimulator of interferon genes (STING) signaling. 2017;292(1):292–304.
Lin Y, Sun Z. Current views on type 2 diabetes. J Endocrinol 2010;204(1):1–11.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103(2):137–49.
WHO. Global report on diabetes: World Health Organization; 2016. 2017.
Verhulst MJ, Loos BG, Gerdes VE, Teeuw W. Evaluating all potential oral complications of diabetes mellitus. Front Endocrinol (Lausanne) 2019;10:56.
Karamitri A, Jockers RJNRE. Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol 2019;15(2):105–25.
Lambrinou E, Hansen TB, Beulens JW. Lifestyle factors, self-management and patient empowerment in diabetes care. Eur J Prev Cardiol 2019;26(2_Suppl):55–63.
Pareek M, Schauer PR, Kaplan LM, Leiter LA, Rubino F, Bhatt DL. Metabolic surgery: weight loss, diabetes, and beyond. 2018;71(6):670–87.
Akbarzadeh A, Norouzian D, Mehrabi M, Jamshidi S, Farhangi A, Verdi AA, et al. Induction of diabetes by streptozotocin in rats. Indian J Clin Biochem 2007;22(2):60–4.
Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 2011;50(5):600–13.
Ali A, Shaheen S, Memon Z, Agha F, Shahid MA, Zahid N. Effects of Diabetogenic Agent Streptozotocin on Hematological Parameters of Wistar Albino Rats “An Experimental Study”. J Adv Med Med Res 2019;6:1–8.
Chandel NS, Avizonis D, Reczek CR, Weinberg SE, Menz S, Neuhaus R, et al. Are metformin doses used in murine cancer models clinically relevant? Cell Metab 2016;23(4):569–70.
Mousavi SM, Niazmand S, Hosseini M, Hassanzadeh Z, Sadeghnia HR, Vafaee F, et al. Beneficial effects of Teucrium polium and metformin on diabetes-induced memory impairments and brain tissue oxidative damage in rats. Int J Alzheimers Dis 2015;2015:493729.
Stepensky D, Friedman M, Raz I, Hoffman A. Pharmacokinetic-pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab Dispos 2002;30(8):861–8.
Ogar I, Egbung GE, Nna VU, Iwara IA, Itam E. Anti-hyperglycemic potential of Hyptis verticillata jacq in streptozotocin-induced diabetic rats. Biomed Pharmacother 2018;107:1268–76.
Foretz M, Guigas B, Viollet B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol 2019;15(10):569–89.
Akhter MS, Uppal P. Toxicity of metformin and hypoglycemic therapies. Adv Chronic Kidney Dis 2020;27(1):18–30.
Malin SK, Kashyap SR. Effects of metformin on weight loss: potential mechanisms. Curr Opin Endocrinol Diabetes Obes 2014;21(5):323–9.
Lv WS, Wen JP, Li L, Sun RX, Wang J, Xian YX, et al. The effect of metformin on food intake and its potential role in hypothalamic regulation in obese diabetic rats. Brain Res 2012;1444:11–9.
Lee CK, Choi YJ, Park SY, Kim JY, Won KC, Kim JY, et al. Intracerebroventricular injection of metformin induces anorexia in rats. Diabetes Metab J 2012;36(4):293–9.
Desilets AR, Dhakal-Karki S, Dunican KC. Role of metformin for weight management in patients without type 2 diabetes. Ann Pharmacother 2008;42(6):817–26.
Kay JP, Alemzadeh R, Langley G, D'angelo L, Smith P, Holshouser SJ. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism 2001;50(12):1457–61.
Harborne LR, Sattar N, Norman JE, Fleming R. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab 2005;90(8):4593–8.
Tilinca MC, Barabas-Hajdu EC, Ferencz GT, Nemes-Nagy E. Involvement of inflammatory cytokines in obesity and its complications. Rev Romana Med Lab 2018;26(3):359–71.
Rehman K, Akash MSH, Alina Z. Leptin: a new therapeutic target for treatment of diabetes mellitus. J Cell Biochem 2018;119(7):5016–27.
Goldberg RB, Mather K. Targeting the consequences of the metabolic syndrome in the Diabetes Prevention Program. Arterioscler Thromb Vasc Biol 2012;32(9):2077–90.
National Collaborating Centre for Chronic Conditions (Great Britain), Chartered Society of Physiotherapy (Great Britain). Multiple sclerosis: national clinical guideline for diagnosis and management in primary and secondary care. In: Royal College of Physicians; 2004.
American Diabetes Association. Executive summary: standards of medical care in diabetes-2010. Diabetes Care 2010;33(1):4–10.