glimepiride

glimepiride
IUPAC name	3-Ethyl-4-methyl-N-[2-(4-{[(4-methylcyclohexyl)carbamoyl]amino}sulfonylphenyl)ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide
Tradename	Amaryl, others
Drugs.com	Monograph
MedlinePlus	a696016
Routes of administration	By mouth
Bioavailability	100%
Protein bound	>99.5%
Metabolism	Liver (CYP2C9)
Elimination half-life	5–8 hours
Excretion	Urine (60%), feces (40%)
CAS number	93479-97-1
PubChem	3476
DrugBank	DB00222
ChemSpiderID	3356
UNII	6KY687524K
KEGG	D00477
ChEBI	5385
ChEMBL	1009
ATC prefix	A10
ATC suffix	BB12

glimepiride is an oral antidiabetic medication of the sulfonylurea class, used in the management of type 2 diabetes mellitus. It functions primarily by stimulating the release of insulin from the pancreatic beta cells. Marketed under brand names such as Amaryl, it is typically prescribed alongside diet and exercise when these measures alone are insufficient for glycemic control.

Medical uses

glimepiride is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It may be used as monotherapy or in combination with other antidiabetic agents, such as metformin or insulin, when dual or triple therapy is required. The American Diabetes Association and other international bodies, including the European Association for the Study of Diabetes, include sulfonylureas like glimepiride in their treatment algorithms. Its use is generally not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Adverse effects

The most common adverse effect associated with glimepiride is hypoglycemia, which can be severe and prolonged, particularly in elderly patients or those with renal impairment. Other reported effects include dizziness, asthenia, headache, and nausea. Less frequently, allergic skin reactions such as urticaria or pruritus may occur. As with other sulfonylureas, there have been post-marketing reports of hepatic porphyria and disulfiram-like reactions with alcohol. The U.S. Food and Drug Administration monitors for serious adverse events, including potential cardiovascular risks debated since the University Group Diabetes Program study.

Pharmacology

Mechanism of action

glimepiride lowers blood glucose by stimulating insulin release from the pancreatic beta cells. It binds to the sulfonylurea receptor subunit of adenosine triphosphate-sensitive potassium channels on the beta cell membrane, leading to channel closure, depolarization, and calcium influx, which triggers exocytosis of insulin granules. It may also have extrapancreatic effects, such as increasing peripheral tissue sensitivity to insulin.

Pharmacokinetics

Following oral administration, glimepiride is completely absorbed, with peak plasma concentrations occurring within 2–3 hours. It is extensively metabolized in the liver primarily by the cytochrome P450 enzyme CYP2C9 to inactive metabolites. The parent drug is highly bound to plasma proteins. Elimination occurs via both renal and hepatic pathways, with a terminal half-life of approximately 5 to 8 hours, allowing for once-daily dosing.

History

glimepiride was developed by the German pharmaceutical company Hoechst AG (later part of Sanofi) and received approval for medical use in the United States in 1995. Its development was part of ongoing research into second-generation sulfonylureas, which aimed to improve upon the safety and pharmacokinetic profiles of earlier agents like chlorpropamide and tolbutamide. The drug's approval was based on clinical trials demonstrating its efficacy in lowering glycated hemoglobin levels.

Society and culture

glimepiride is available under various brand names globally, including Amaryl (marketed by Sanofi) and numerous generic versions. It is on the World Health Organization's List of Essential Medicines. The cost of therapy varies widely, with generic formulations significantly reducing the economic burden on healthcare systems like the National Health Service in the United Kingdom. Its use is sometimes debated in the context of newer antidiabetic drug classes, such as SGLT2 inhibitors and GLP-1 receptor agonists, which may offer cardiovascular benefits.

Category:Antidiabetic drugs Category:Sulfonylureas Category:World Health Organization essential medicines