• P-ISSN 0973-7200 E-ISSN 2454-8405
  • Follow us

Journal of Pharmaceutical Research


Effect of Candesartan cilexetil on the Blood Glucose Levels of Glimepiride in Normal and Diabetic Albino Rats
  • VIEWS 522
  • PDF 215

Journal of Pharmaceutical Research

Year: 2018, Volume: 17, Issue: 2, Pages: 57-66

Original Article

Effect of Candesartan cilexetil on the Blood Glucose Levels of Glimepiride in Normal and Diabetic Albino Rats


Background: Co administration of two or more medications to a patient is called polypharmacy. Hence, much attention is required to study the possible drug interaction in the prescription, to reduce the influence of one drug action on the another. Accordingly, the effect of candesartan cilexetil was studied on the blood glucose levels of glimepiride treated normal and diabetic rats. Method: Effect of blood glucose levels were studied by using Candesartan cilexetil and Glimepiride in normal and diabetic albino male rats at a dose of 1.44 mg/kg and 0.09 mg/kg, respectively. The blood samples were collected during the study at the time intervals of 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours. The samples were subjected to estimation of blood glucose levels using glucometer. Results: The present study was conducted in both normal and diabetic rats. Glimepiride showed its hypoglycemic effect at the 4th hour, whereas candesartan cilexetil doesn�t show any changes in blood glucose levels in both normal and diabetic rats. In normal rats, candesartan cilexetil doesn�t affect on the blood glucose levels of glimepiride in both single and multiple dose studies. In diabetic rats, the candesartan cilexetil showed significant action on blood glucose levels of glimepiride in multiple dose interaction study but the insignificant effect of candesartan cilexetil in single dose interaction on glimepiride. Hence, the interaction was carefully monitored in type-2 diabetes mellitus patients. Conclusion: The study suggested that candesartan cilexetil has a profound effect on blood glucose levels of glimepiride on long term use; the possible mechanism for the cause is either angiotensin converting enzyme inhibitors improve insulin sensitivity or inhibition of CYP2C9. The study also recommended that caution must be taken while prescribing with the combination of candesartan cilexetil and glimepiride or its analogs.


  • Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. The American journal of geriatric pharmacotherapy. 2007 Dec 1; 5(4):345-51.
  • Prescott LF. Clinically important drug interactions. Drugs. 1973 Mar 1; 5(3):161-86.
  • American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes care. 2014 Jan 1; 37 (Supplement 1):S81-90.
  • Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Annals of internal medicine. 2003 Nov 4; 139(9):761-76.
  • Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension. 1992 May 1; 19(5):403-18.
  • Sowers JR, Epstein M. Diabetes mellitus and hypertension, emerging therapeutic perspectives. Cardiovascular Therapeutics. 1995 Jun 1;13 (2):149-210.
  • Solini A, DeFronzo RA. Hypertension, cardiovascular disease, diabetes mellitus, and diabetic nephropathy: role of insulin resistance. InThe Kidney and Hypertension in Diabetes Mellitus 1996 (pp. 61-74). Springer US.
  • Van Booven D, Marsh S, McLeod H, Carrillo MW, Sangkuhl K, Klein TE, Altman RB. Cytochrome P450 2C9-CYP2C9. Pharmacogenetics and genomics. 2010 Apr;20(4):277.
  • Murakami H, Yabusaki Y, Ohkawa H. Expression of rat NADPH-cytochrome P-450 reductase cDNA in Saccharomyces cerevisiae. DNA. 1986 Feb;5(1):1-0.
  • Holstein A, Beil W, Kovacs P. CYP2C metabolism of oral antidiabetic drugs-impact on pharmacokinetics, drug interactions and pharmacogenetic aspects. Expert opinion on drug metabolism & toxicology. 2012 Dec 1;8 (12):154963.
  • Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy. 2016 Mar;7(2):27.
  • Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabetic medicine. 2005 Apr 1; 22(4):359-70.
  • Etuk EU. Animals models for studying diabetes mellitus. Agric Biol JN Am. 2010;1(2):130-4.
  • Ghosh M. Fundamentals of Experimental Pharmacology Hilton and Company. Kolkata, India. 2005.
  • Korytkowski M, Thomas A, Reid L, Tedesco MB, Gooding WE, Gerich J. Glimepiride improves both first and second phases of insulin secretion in type 2 diabetes. Diabetes Care. 2002 Sep 1;25 (9):1607-11.
  • Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes. Diabetes care. 2005 Dec 1;28(12):2948-61.
  • Prasad A, Quyyumi AA. Renin-angiotensin system and angiotensin receptor blockers in the metabolic syndrome. Circulation. 2004 Sep 14;110 (11):1507-12.
  • Kurtz TW, Pravenec M. Antidiabetic mechanisms of angiotensinconverting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin�angiotensin system. Journal of hypertension. 2004 Dec 1;22(12):2253-61.
  • Higashiura K, Ura N, Takada T, Li Y, Torii T, Togashi N, Takada M, Takizawa H, Shimamoto K. The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats.
  • Onuchin SG, Elsukova OS, Onuchina EL. Potential of combined hypoglycemic, antihypertensive, and hypolipidemic therapy in patients with diabetes mellitus and diabetic foot syndrome. Klinicheskaia meditsina. 2007 Dec;86 (8):61-6.
  • Srivastava RA. Fenofibrate ameliorates diabetic and dyslipidemic profiles in KKAy mice partly via down-regulation of 11?-HSD1, PEPCK and DGAT2: Comparison of PPAR?, PPAR?, and liver x receptor agonists. European journal of pharmacology. 2009 Apr 1;607(1):258-63.
  • Murayama S, Hirano T, Sakaue T, Okada K, Ikejiri R, Adachi M. Low-dose candesartan cilexetil prevents early kidney damage in type 2 diabetic patients with mildly elevated blood pressure. Hypertension Research. 2003;26(6):453-8.
  • Rosei EA, Rizzoni D, Muiesan ML, Sleiman I, Salvetti M, Monteduro C, Porteri E, CENTRO (CandEsartaN on aTherosclerotic Risk factors) Study Investigators. Effects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus. Journal of hypertension. 2005 Feb 1; 23(2):435-44.
  • Sj�lie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, Bilous R, Chaturvedi N, DIRECT Programme Study Group. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. The Lancet. 2008 Oct 24; 372 (9647):1385-93.
  • DIRECT Programme Study Group, Chaturvedi N. The Diabetic Retinopathy Candesartan Trials (DIRECT) programme, rationale and study design. Journal of the Renin-Angiotensin-Aldosterone System. 2002 Dec; 3(4):255-61.
  • DIRECT Programme Study Group. The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme:baseline characteristics. Journal of the Renin-AngiotensinAldosterone System. 2005 Mar; 6(1):25-32.
  • Grassi G, Seravalle G, Dell�Oro R, Trevano FQ, Bombelli M, Scopelliti F, Facchini A, Mancia G. Comparative effects of candesartan and hydrochlorothiazide on blood pressure, insulin sensitivity, and sympathetic drive in obese hypertensive individuals: results of the CROSS study. Journal of hypertension. 2003 Sep 1; 21 (9):1761-9.
  • Chu KY, Lau T, Carlsson PO, Leung PS. Angiotensin II type 1 receptor blockade improves ?-cell function and glucose tolerance in a mouse model of type 2 diabetes. Diabetes. 2006 Feb 1; 55 (2):367-74.
  • Ramracheya RD, Muller DS, Wu Y, Whitehouse BJ, Huang GC, Amiel SA, Karalliedde J, Viberti G, Jones PM, Persaud SJ. Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans. Diabetologia. 2006 Feb 1; 49(2):321-31.
  • Lau T, Carlsson PO, Leung PS. Evidence for a local angiotensingenerating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets. Diabetologia. 2004 Feb 1; 47(2):240-8.
  • Tikellis C, Wookey PJ, Candido R, Andrikopoulos S, Thomas MC, Cooper ME. Improved islet morphology after blockade of the renin-angiotensin system in the ZDF rat. Diabetes. 2004 Apr 1;53(4):989-97.
  • Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus: part 1. A meta-analysis of randomised clinical trials. Diabetes & metabolism. 2004 Dec 1; 30(6):487-96.
  • Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI, Cooper ME. Why blockade of the renin�angiotensin system reduces the incidence of new-onset diabetes. Journal of hypertension. 2005 Mar 1; 23(3):463-73.
  • Putnam K, Shoemaker R, Yiannikouris F, Cassis LA. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. American Journal of Physiology-Heart and Circulatory Physiology. 2012 Mar 15; 302 (6):H1219-30.
  • Scheen AJ. Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system. Drugs. 2004 Nov 1; 64 (22):2537-65.


Subscribe now for latest articles and news.