Gliclazide, sold under the brand nameDiamicron among others, is a sulfonylurea type ofanti-diabetic medication, used to treattype 2 diabetes.[7] It is used when dietary changes, exercise, and weight loss are not enough.[4] It is taken by mouth.[7]
Gliclazide is used for control of hyperglycemia in gliclazide-responsivediabetes mellitus of stable, mild, non-ketosis prone, type 2 diabetes. It is used when diabetes cannot be controlled by proper dietary management and exercise and when metformin has already been tried.[11]
National Kidney Foundation (2012 Update) claims that Gliclazide does not requiredosage up titration even in end stage kidney disease.
Hypoglycemia (11 - 12%) - while it was shown to have the same efficacy as glimepiride, one of the newer sulfonylureas, the European GUIDE study has shown that it has approximately 50% less hypoglycemic confirmed episodes in comparison with glimepiride.[14]
Gliclazide selectively binds to sulfonylurea receptors (SUR-1) on the surface of the pancreatic beta-cells. It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors (SUR-2A) in the heart.[17] This binding effectively closes these K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocytosis of insulin vesicles leading to insulin release.[18]
The mouse model ofMaturity-onset diabetes of the young (MODY) diabetes suggested that the reduced gliclazide clearance stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently and that there was no consistent decrease in gliclazide clearance in randomly selected HNF1A-MODY and HNF4A-MODY patients.[19]
Its classification has been ambiguous, as literature uses it as both a first-generation[20] and second-generation[21] sulfonylurea.
According to the Biopharmaceutical Classification System (BCS), gliclazide falls under the BCS Class II drug, which is poorly soluble and highly permeable.
Gliclazide undergoes extensive metabolism to several inactive metabolites in human beings, mainly methylhydroxygliclazide and carboxygliclazide. CYP2C9 is involved in the formation of hydroxygliclazide in human liver microsomes and in a panel of recombinant human P450s in vitro.[23][24] But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.[25][26]
^World Health Organization (2019).World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization.hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^abcd"Gliclazide".Lexicomp. Wolters Kluwer N.V.Archived from the original on 2 June 2023. Retrieved1 June 2023.
^Schernthaner G, Grimaldi A, Di Mario U, Drzewoski J, Kempler P, Kvapil M, et al. (August 2004). "GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients".European Journal of Clinical Investigation.34 (8):535–542.doi:10.1111/j.1365-2362.2004.01381.x.hdl:1874/10657.PMID15305887.S2CID13636359.
^Mégarbane B, Chevillard L, Khoudour N, Declèves X (April 2022). "Gliclazide disposition in overdose - a case report with pharmacokinetic modeling".Clinical Toxicology.60 (4):541–542.doi:10.1080/15563650.2021.1993245.PMID34698608.S2CID239887850.
^Mégarbane B, Chevillard L, Khoudour N, Declèves X (April 2022). "Gliclazide disposition in overdose - a case report with pharmacokinetic modeling".Clinical Toxicology.60 (4):541–542.doi:10.1080/15563650.2021.1993245.PMID34698608.S2CID239887850.
^Urbanova J, Andel M, Potockova J, Klima J, Macek J, Ptacek P, et al. (2015). "Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model".Current Pharmaceutical Design.21 (39):5736–5748.doi:10.2174/1381612821666151008124036.PMID26446475.
^Ballagi-Pordány G, Köszeghy A, Koltai MZ, Aranyi Z, Pogátsa G (January 1990). "Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds".Diabetes Research and Clinical Practice.8 (2):109–114.doi:10.1016/0168-8227(90)90020-T.PMID2106423.
^Shimoyama T, Yamaguchi S, Takahashi K, Katsuta H, Ito E, Seki H, et al. (June 2006). "Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation".Metabolism.55 (6):722–730.doi:10.1016/j.metabol.2006.01.019.PMID16713429.
^Mégarbane B, Chevillard L, Khoudour N, Declèves X (April 2022). "Gliclazide disposition in overdose - a case report with pharmacokinetic modeling".Clinical Toxicology.60 (4):541–542.doi:10.1080/15563650.2021.1993245.PMID34698608.S2CID239887850.
^Rieutord A, Stupans I, Shenfield GM, Gross AS (December 1995). "Gliclazide hydroxylation by rat liver microsomes".Xenobiotica; the Fate of Foreign Compounds in Biological Systems.25 (12):1345–1354.doi:10.3109/00498259509061922.PMID8719909.
