Actions and Spectrum: 

glimepiride works by attaching to the ATP-sensitive potassium channels on the surface of pancreatic beta cells and causing them to close. The cell membrane depolarizes as a result of this closure, which leads to the release of insulin. 

glimepiride’s effect range is rather small; therefore, its main effects are on insulin and blood sugar levels. Other areas of metabolism or body processes are not significantly impacted. I

t is crucial to remember that glimepiride might result in hypoglycaemia (low blood sugar) as an adverse reaction, thus it must be taken carefully and with a doctor’s supervision. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency Defined  

1-10% 

Headache (1.5%) 

Asthenia (1.6%) 

Nausea (1.1%) 

Dizziness (1.7%) 

>10% 

Hypoglycemia (4-20%) 

<1% 

Pruritus 

Urticaria 

Allergic skin reactions 

Erythema 

Morbilliform or maculopapular eruptions 

Diarrhea 

Vomiting 

Agranulocytosis 

Gastrointestinal pain 

Anemia 

Elevation of liver enzyme levels 

Hepatic porphyria reactions 

Leukopenia 

Pancytopenia 

Thrombocytopenia, hemolytic 

Disulfiram-like reactions 

Hyponatremia 

Aplastic anemia 

Cholestasis 

Jaundice (rare) 

Post marketing reports 

Hemolytic anemia in patients with and without G6PD deficiency 

Hepatic impairment (e.g., jaundice, cholestasis), as well as hepatitis, which may progress to liver failure 

Serious hypersensitivity reactions, including angioedema, anaphylaxis, and Stevens- Johnson Syndrome 

Aplastic anemia, pancytopenia, Leukopenia, and agranulocytosis 

Hyponatremia and SIADH, most often in patients on other medications or increase release of antidiuretic hormone or have medical conditions known to cause hyponatremia 

Porphyria cutanea tarda, photosensitivity reactions and allergic vasculitis 

Dysgeusia 

Alopecia 

Thrombocytopenia (including severe cases with platelet count <10,000/mcL) and thrombocytopenic purpura 

Hepatic porphyria reactions and disulfiram-like reactions 

Black Box Warning 

According to the glimepiride black box warning, significant hypoglycaemia (low blood sugar) may occur, which can result in a coma or even death.

When glimepiride is used with certain other drugs, such as insulin or other sulfonylureas, or in those with kidney or liver disease, hypoglycaemia is more likely to happen. 

The warning also advises against using glimepiride in people with type 1 diabetes or diabetic ketoacidosis as the drug is ineffective in these situations. 

Contraindication/Caution: 

Contraindication: 

• glimepiride or other sulfonylureas hypersensitivity 
• diabetes type 1 
• ketoacidosis in diabetics 
• serious renal or liver illness 

Caution: 

• glimepiride is not advised to be used during pregnancy or during nursing since it might enter the breast milk and damage the unborn child. 
• Those over the age of 65 may require a different dosage of glimepiride because they may be more sensitive to its side effects. 
• glimepiride has the potential to produce hypoglycaemia, especially in people with liver or renal disease and when used with other drugs that drop blood sugar. 
• glimepiride may need to be temporarily discontinued during surgery or a condition that impairs appetite or raises the risk of hypoglycaemia. 
• Alcohol should be avoided or consumed in moderation when taking glimepiride as it may increase the risk of hypoglycaemia. 

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology 

A second-generation sulfonylurea anti-diabetic medication called glimepiride increases the amount of insulin that the pancreatic beta cells secrete. It blocks the ATP-sensitive potassium channels (KATP) via binding to the sulfonylurea receptor (SUR) on the surface of pancreatic beta cells, which causes the membrane to depolarize and release insulin. 

Pharmacodynamics 

glimepiride’s effects on the pancreatic beta cells boost insulin production, which lowers blood glucose levels in people with type 2 diabetes mellitus. In reaction to glimepiride, the pancreatic beta cells produce insulin in a glucose-dependent way. As a result, the medication only promotes insulin release when blood glucose levels are high, assisting in the prevention of hypoglycemia. 

Pharmacokinetics 

Absorption   

Orally given glimepiride is quickly absorbed from the digestive tract. Almost 100% of the medication’s dosage is absorbed into the circulation, which indicates that the drug has a high bioavailability. To promote the best absorption, glimepiride should be taken with the first substantial meal of the day. 

Distribution 

More than 99% of glimepiride is protein-bound to serum albumin. It has a substantial volume of distribution, which suggests that it is dispersed among the tissues of the body. 

Metabolism 

The cytochrome P450 enzyme system, CYP2C9, largely metabolizes glimepiride in the liver. The inactive hydroxy derivative is the main metabolite. The carboxyl derivative and the cyclohexyl hydroxy methyl derivative are two further minor metabolites. 

Elimination and excretion 

glimepiride and its byproducts are eliminated in the feces (40%) and urine (60%) respectively. The medicine has an elimination half-life of around 5 to 9 hours, and total elimination happens 4 to 5 days following the last dose. 

Administration:  

glimepiride pills are taken orally to provide the medication. To achieve the best absorption, it is normally taken once daily with the first large meal of the day.

The pills should not be chewed, crushed, or broken and should be consumed whole with a glass of water. glimepiride dose is tailored to the patient’s glycaemic control and should be progressively increased to reach the desired blood glucose level. 

Patient information leaflet 

Generic Name: glimepiride 

Why do we use glimepiride? 

glimepiride is used to treat type 2 diabetes mellitus, a disease where the body has trouble using insulin properly and has high blood sugar levels as a result. By encouraging the secretion of insulin from the pancreas, the medication is used to assist in lowering blood glucose levels.