Main Article Content
Aim: The complications associated with diabetes and the new trend of using combination therapy in the management of the disease gave birth to this work, aimed at assessing the hepatotoxic and nephrotoxic effects of selected popularly used antidiabetic medications in type 2 diabetic patients within Ota, Ogun State, Nigeria.
Study Design: The participants, diabetic (n=195) and non-diabetic (n=30) were divided into the following groups based on their medications: 1 (Non Diabetic control), 2 (Metformin), 3 (Glimepiride), 4 (Glibenclamide), 5 (Metformin and Glimepiride), 6 (Meformin and Glibenclamide), 7 (Metformin, Glimepiride and Glibenclamide) and 8 (Diabetic Dietary control).
Methodology: Serum protein expression profiling, liver and kidney function parameters were assessed in participant’s blood using Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and standard laboratory methods respectively.
Results: Glyceamic control within the diabetic groups was 29.23%. Urea concentration was significantly increased (p < 0.05) in groups 5 and 7 compared with groups 1 and 8 while the serum creatinine levels in the different groups showed no significant difference. Activities of alkaline phosphatase and aspartate aminotransferase increased significantly (p < 0.05) in group 5 compared with groups 1 and 8. A low molecular weight protein likely to be Leptin (molecular weight 18 kDa) was over-expressed in all the diabetic groups.
Conclusion: This study shows that use of multiple rather than single drugs caused significant functional changes in the liver and kidney. The control of diabetes may best be carried out with dietary control and lifestyle modification as well as good therapeutic drug monitoring for safe assessment of baseline organ function.
American Diabetes Association (ADA). Diagnosing and classification of diabetes. Diab Car. 2006;29(1):51–580.
American Diabetes Association (ADA). Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(1):S13- S27.
World Health Organization (WHO). Population ageing—A public health challenge. Geneva; 1998.
[Accessed 9 September, 2019]
International Diabetes Federation, IDF Diabetes Atlas: Africa. Fifth edition; 2011.
World Health Organization (WHO). Diabetes Mellitus. World Health Organization Fact Sheet. 1999;138.
[Accessed 7 march, 2019]
Vagula M, Devi SS. Hepatotoxicity of antidiabetic drugs. US Pharmac. 2008; 33(5):3-9.
International Diabetes Federation (IDF). IDF Diabetes Atlas: Global. Seventh Edition. 2015;1-144.
Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicolog Sci. 2002;65:166-176.
Friedman SE, Grendell JH, McQuaid KR. Current diagnosis and treatment in gastroenterology. In: Lang Medical Books. New York: McGraw-Hill. 2003;664–679.
Huerta C, Zhao SZ, Garcia-Rodriguez LA. Risk of acute liver injury in patients with diabetes. Pharmacoth. 2002;22:1091-1096.
Naughton CA. Drug-induced nephrotoxi-city. Amer Fam Phys. 2008;78:743-750.
Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. The New Eng J Med. 2011; 365:2002-2012.
Adisa R, Alutundu, MB, Fakeye TO. Factors contributing to nonadherence to oral hypoglycemic medications among ambulatory type 2 diabetes patients in Southwestern Nigeria. Pharm Pract. 2009; 7:163-169.
Janairo G, Linley MS, Yap L, Llanos-Lazaro N, Robles J. Determination of the sensitivity range of biuret Test for undergraduate biochemistry experiments. e-Jour Sci and Tech. 2011;5(22):77-83.
Hou YC, Chang YL, Kuo SC, Chiang CF, Chiang CY, Lin YF, Weng PC, Hu FC, Wu JH, Lai CH. Serum hyperglycemia might be not related to fat composition of diet and vegetable composition of diet might improve sugar control in taiwanese diabetic subjects. Internat J Med Sci. 2014; 11:515-521.
Mengjun HU, Isaacson JH. A 48-year-old man with uncontrolled diabetes. Clevel Clin J Med. 2009;76(7):413-416.
Stefan HR, Marggraf GN, Johannes HS, Frauke GR, Frank P, Janssen O, Thomas P, Andreas K. Early detection of acute renal failure by serum cystatin C. Kid Internat. 2004;66:115–1122.
Thomsen HS, Judith FS, Webb JA. Contrast medium-induce nephropathy. Med Radiol. 2014;5:81-104.
Zanchi A, Lehmann R, Philippe J. Antidiabetic drugs and kidney disease-recommendations of the Swiss Society for Endocrinology and Diabetology. Swis Med Week. 2012;142:w13629.
Strugaru AM, Botnariu G, Agoroaei L, Grigorium IC, Butnaru E. Metformin induced lactic acidosis--particularities and course. Rev Med Chir Soc Med Nat Lasi. 2013;117:1035-1042.
Diwan V, Gobe G, Brown L. Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease. Pharmacol Res. 2014;79:104-110.
Kakadiya J, Rathod SP. Protective effect of glimepiride alone and its combination with metformin on serum glucose, HbA1c and liver functions in nondiabetic and diabetic rats. Pharmacol On Lin. 2009;2:261-272.
Ali T, Bhalli JA, Rana SM, Khan QM. Cytogenic damage in female Pakistan agricultural workers exposed to pesticides. Environ and Mol Muta. 2008;49(5):374-380.
Cone CJ, Bachyrycz AM, Murata GH. Hepatotoxicity associated with metformin therapy in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease. The Ann Pharmacol. 2010;44: 1655-1659.
Chounta A, Zouridakis S, Ellinas C, Tsiodras S, Zoumpouli C, Kopanakis S, Giamarellou H. Cholestatic liver injury after glimepiride therapy. J Hep. 2005;42:944-946.
Friedman LS, Martin P, Munoz SZ. Liver function tests and the objective evaluation of the patient with liver disease. In: A textbook of liver disease, eds. Zakin D, Boyer TD. 3rd ed. Hepatology. Philadelphia: WB Saunders. 1996;791-833.
Kumar RS, Gupta M, Mazumdar UK, Rajeshwar Y, Kumar TS, Gomath P, Roy R. Effects of methanol extracts of Caesalpinia bonducella and Bauhinia racemosa on hematology and hepatorenal function in mice. The J Toxicol Sci. 2005; 30:265-274.
Riaz S, Alam SS, Raza M, Hasnain S, Akhtar MW. Obesity as risk factor and study of obesity related proteins in diabetes mellitus. Afri J Biotechnol, 2009; 8(5):737-744.
Ebtesam AA, Adeeb S. Leptin, resistin and visfatin: The missing link between endocrine metabolic disorders and immunity. Eur J Med Res. 2013;8(1):12.
Lakka HM, Lakka TA, Tuomilehto J, Salonen JT. Abdominal obesity is associated with increased risk of acute coronary events in men. Europ Hear J. 2002;23:706-713.