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Trade names | Diamicron, Diaprel, Azukon, others [1] |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
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Routes of administration | By mouth |
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Elimination half-life | 10.4 hours |
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ECHA InfoCard | 100.040.221 |
Chemical and physical data | |
Formula | C15H21N3O3S |
Molar mass | 323.41 g·mol−1 |
3D model (JSmol) | |
Melting point | 180 to 182 °C (356 to 360 °F) |
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Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat type 2 diabetes. [7] It is used when dietary changes, exercise, and weight loss are not enough. [4] It is taken by mouth. [7]
Side effect may include low blood sugar, vomiting, abdominal pain, rash, and liver problems. [4] [7] Use by those with significant kidney problems or liver problems or who are pregnant is not recommended. [7] [4] Gliclazide is in the sulfonylurea family of medications. [7] It works mostly by increasing the release of insulin. [7]
Gliclazide was patented in 1966 and approved for medical use in 1972. [8] It is on the World Health Organization's List of Essential Medicines. [9] It is not available for sale in the United States. [10]
Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes 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 require dosage up titration even in end stage kidney disease.
Common adverse effects over 10%: [13]
Uncommon adverse effect between 1 - 10%: [13]
Rare adverse effects (under 1%): [13]
Hyperglycemic action may be caused by danazol, chlorpromazine, glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic action may be potentiated by phenylbutazone, alcohol, fluconazole, β-blockers, and possibly ACE inhibitors. It has been found that rifampin increases gliclazide metabolism in humans in vivo. [15]
Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and Monitoring. [16]
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 of Maturity-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.
Water solubility = 0.027mg/L[ citation needed ]
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]
Hypoglycemia, also spelled hypoglycaemia or hypoglycæmia, sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.
Glimepiride is an antidiabetic medication within the sulfonylurea class, primarily prescribed for the management of type 2 diabetes. It is regarded as a second-line option compared to metformin, due to metformin's well-established safety and efficacy. Use of glimepiride is recommended in conjunction with lifestyle modifications such as diet and exercise. It is taken by mouth, reaching a peak effect within three hours and lasting for about a day.
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, and is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotic medication. It has been shown to inhibit inflammation, and is not associated with weight gain. Metformin is taken by mouth.
Drugs used in diabetes treat types of diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.
Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, a dehydrogenated derivative of urea). The side chains R1 and R2 distinguish various sulfonylureas. Sulfonylureas are the most widely used herbicide.
ATC code A10Drugs used in diabetes is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup A10 is part of the anatomical group A Alimentary tract and metabolism.
Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. Along with neonatal diabetes, MODY is a form of the conditions known as monogenic diabetes. While the more common types of diabetes involve more complex combinations of causes involving multiple genes and environmental factors, each forms of MODY are caused by changes to a single gene (monogenic). HNF1A-MODY are the most common forms.
Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals. According to the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP), and based on a sample examined between 2004 and 2005, an estimated 55,819 cases involved insulin, and severe hypoglycemia is likely the single most common event.
Tolbutamide is a first-generation potassium channel blocker, sulfonylurea oral hypoglycemic medication. This drug may be used in the management of type 2 diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas.
Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.
Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin.
Gliquidone is an anti-diabetic medication in the sulfonylurea class. It is classified as a second-generation sulfonylurea. It is used in the treatment of diabetes mellitus type 2. It is marketed by the pharmaceutical company Boehringer Ingelheim (Germany).
HNF1 homeobox A, also known as HNF1A, is a human gene on chromosome 12. It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes. Mutations in the HNF1A gene have been known to cause diabetes. The HNF1A gene also contains a SNP associated with increased risk of coronary artery disease.
ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.
As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. Insulin is also used along with glucose to treat hyperkalemia. Typically it is given by injection under the skin, but some forms may also be used by injection into a vein or muscle. There are various types of insulin, suitable for various time spans. The types are often all called insulin in the broad sense, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. It is on the World Health Organization's List of Essential Medicines. In 2022, it was the 192nd most commonly prescribed medication in the United States, with more than 2 million prescriptions.
MODY 1 or HNF4A-MODY is a form of maturity onset diabetes of the young.
MODY 3 or HNF1A-MODY is a form of maturity-onset diabetes of the young. It is caused by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is the most common type of MODY in populations with European ancestry, accounting for about 70% of all cases in Europe. HNF1α is a transcription factor that is thought to control a regulatory network important for differentiation of beta cells. Mutations of this gene lead to reduced beta cell mass or impaired function. MODY 1 and MODY 3 diabetes are clinically similar. About 70% of people develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often be treated with sulfonylureas with excellent results for decades. However, the loss of insulin secretory capacity is slowly progressive and most eventually need insulin.
Gemigliptin (rINN), sold under the brand name Zemiglo, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 inhibitor class of drugs. Glucose lowering effects of DPP-4 inhibitors are mainly mediated by GLP-1 and gastric inhibitory polypeptide (GIP) incretin hormones which are inactivated by DPP-4.
Glybuzole is a hypoglycaemic medicine, mainly used to treat diabetes mellitus type 2. It is an oral antidiabetic drug (OAD), when administered in the right dose it will help bring the blood glycose level down by stimulating the insulin production. Similar medicines are glimepiride, glipizide, glibenclamide, gliclazide, and gliquidone.