Investigational Drug Details
| Drug ID: | D153 |
| Drug Name: | Gliclazide |
| Synonyms: | 1-(3-azabicyclo(3.3.0)oct-3-yl)-3-(p-tolylsulfonyl)urea; 1-(hexahydrocyclopenta(c)pyrrol-2(1H)-yl)-3-(p-tolylsulfonyl)urea; Gliclazide |
| Type: | Chemical drug |
| DrugBank ID: | DB01120 |
| DrugBank Description: | Gliclazide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It has been classified differently according to its drug properties in which based on its chemical structure, gliclazide is considered a first-generation sulfonylurea due to the structural presence of a sulfonamide group able to release a proton and the presence of one aromatic group. On the other hand, based on the pharmacological efficacy, gliclazide is considered a second-generation sulfonylurea which presents a higher potency and a shorter half-life. Gliclazide belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%). |
| PubChem ID: | 3475 |
| CasNo: | 21187-98-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | N(C(=O)NS(=O)(=O)c1ccc(cc1)C)N1CC2C(C1)CCC2 |
| Structure: |
|
| InChiKey: | BOVGTQGAOIONJV-UHFFFAOYSA-N |
| Molecular Weight: | 323.418 |
| DrugBank Targets: | ATP-binding cassette sub-family C member 8 binder; Vascular endothelial growth factor A other/unknown |
| DrugBank MoA: | Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules. |
| DrugBank Pharmacology: | Based on the pharmacological properties, gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics. |
| DrugBank Indication: | For the treatment of NIDDM in conjunction with diet and exercise. |
| Targets: | VEGFA other/unknown |
| Therapeutic Category: | Antidiabetic drug |
| Clinical Trial Progress: | Phase 4 completed (NCT03068065) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0081 | NCT03068065 | Phase 4 | Completed | No Results Available | May 2014 | March 1, 2017 | Details |
| L0893 | ChiCTR-TRC-14004660 | Post-market | Not Recruiting | No Results Available | 21/09/2014 | 18 April 2017 | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00255 | 35163991 | Molecules | Sitagliptin Is More Effective Than Gliclazide in Preventing Pro-Fibrotic and Pro-Inflammatory Changes in a Rodent Model of Diet-Induced Non-Alcoholic Fatty Liver Disease. | Details |
| A03840 | 33852508 | Eur J Gastroenterol Hepatol | The role of nursing care in the type 2 diabetes treatment associated with chronic liver diseases. | Details |
| A13467 | 29957886 | J Diabetes Investig | Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial. | Details |
| A16533 | 28332301 | J Diabetes | Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease. | Details |
| A18741 | 26976710 | Endocrinol Nutr | Effect of incretin therapies compared to pioglitazone and gliclazide in non-alcoholic fatty liver disease in diabetic patients not controlled on metformin alone: An observational, pilot study. | Details |
| A51891 | 33432553 | J Endocrinol Invest | Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care. | Details |