Glimepiride

BRAND NAMES:

DUETACT: Glimepiride 2 mg and pioglitazone 30 mg, two oral diabetic drugs that help control blood sugar levels, are combined in Duetact. It is also used together with diet and exercise to help people with type 2 diabetes mellitus better control their blood sugar levels.

AMARYL: This tablet stimulates the production of insulin in your body (pancreas). The insulin then lowers the blood glucose level. The available dosage is 1 mg, 2 mg, and 4 mg (Glimepiride).

Glycomet Trio: Glycomet Trio contains Glimepiride, Metformin, and Voglibose, a combination of three anti-diabetic medicines.

Glycomet GP: It is the combination of two medicines, glimepiride and metformin, used to treat type 2 diabetes mellitus.

MECHANISM OF ACTION:

Glimepiride is an insulin secretagogue that, like other sulfonylureas, works only in people with residual pancreatic beta-cell function. They act on ATP-dependent potassium channels on the cell membrane of pancreatic beta cells, resulting in iatrogenic depolarisation by preventing potassium from leaving the cell. The depolarisation activates voltage-dependent calcium channels on the cell membrane, causing an increase in intracellular calcium and subsequent insulin exocytosis into the bloodstream. Insulin then works on cell membrane receptors, activating GLUT-4 expression and glucose transport into the cell, reducing blood glucose levels. Furthermore, studies have demonstrated that glimepiride interacts with Epac3, a nucleotide exchanger that regulates insulin granule exocytosis. Glimepiride's efficacy was shown in a study on healthy individuals. The results revealed a linear association between serum glimepiride and insulin release in euglycemic and hyperglycaemic circumstances.

PHARMACOKINETICS:

Absorption: Glimepiride is totally absorbed within one hour after oral dosing and has a linear pharmacokinetic profile. After a single oral dose of glimepiride in healthy patients and several oral doses with type 2 diabetes, the peak plasma concentrations (Cmax) were attained after 2 to 3 hours post-dose.

Distribution: In healthy subjects, the volume of distribution following intravenous injection was 8.8 L (113 mL/kg), with 99.5% bound to plasma protein.

Metabolism: It has been observed that glimepiride is metabolised in the liver. After an intravenous or oral dosage, glimepiride undergoes oxidative biotransformation via the CYP2C9 enzyme to produce a pharmacologically active main metabolite, cyclohexyl hydroxymethyl derivative (M1). One or more cytosolic enzymes can convert M1 into the inactive metabolite carboxyl derivative (M2). M1 preserved around one-third of its parent's pharmacologic action in an animal model, with a half-life of 3-6 hours. It remains unclear if M1's glucose-lowering action is clinically significant.

Elimination:

• Half-life: 5-9 hours
• Total body clearance: 47.8 mL/min
• Excretion: Urine 60% and Faeces 40%

PHARMACODYNAMICS:

Glimepiride is a second-generation sulfonylurea anti-diabetic medication. It decreases blood glucose levels, like other sulfonylurea medications, by blocking ATP-dependent potassium channels in pancreatic beta cells, which restores insulin production. This effect is dependent on functional beta cells in the pancreatic islets. Sulfonylurea targets the ATP-sensitive K+ channels and four inwardly rectifying K+ channel subunits. Sulfonylureas bind to the Sulfonylurea receptor subunit of the channel, resulting in channel closure. The closure of KATP channels depolarises the plasma membrane, causing the activation of voltage-dependent Ca2+ channels, resulting in an influx of extracellular Ca2+, which causes exocytosis and insulin release from insulin-containing granules in pancreatic beta cells. Secreted insulin can bind to receptors, activating the PI3/Akt pathway and transcription factors in beta cells that govern insulin production.

DOSAGE AND ADMINISTRATION

The standard starting dose of glimepiride is 1 to 2 mg once daily, taken orally before the patient's first meal. Patients who are prone to hypoglycemia should start with 1 mg once daily and gradually increase to the appropriate amount. Following initial therapy, the usual maintenance dosage is 1 to 4 mg once a day; however, this can be increased slowly to 8 mg once daily based on the patient's blood glucose and haemoglobin A1c levels. It is important to note that current guidelines do not specify a fixed dosage regimen for glimepiride, and the dose must be adjusted based on the patient's blood glucose levels and haemoglobin A1c.

CONTRAINDICATIONS:

Glimepiride is contraindicated in the following patient categories and conditions:

• Diabetic ketoacidosis
• Type 1 diabetic mellitus
• Hypersensitivity to glimepiride

DRUG INTERACTIONS:

Drugs that affect glucose regulation may interact with glimepiride. Insulin and other anti-diabetic drugs mix with glimepiride to generate a hypoglycemic effect. These medications, when used together, have the potential to reduce blood sugar to the point of hypoglycemia. Some medications can enhance glimepiride's glucose-lowering action, while others can reduce it. The medicines listed below can impair the efficacy of sulfonylures.

• atypical antipsychotics (such as olanzapine and clozapine)
• Thiazide and other diuretics
• corticosteroids
• oestrogens

SIDE EFFECTS:

Glimepiride's common side effects include

• wheezing
• dizziness
• skin rash
• fast heartbeat
• hives
• itching
• tightness in the chest
• Difficulty with swallowing
• unusual weakness

TOXICITY:

Hypoglycemia can result from using too many sulfonylureas, such as glimepiride. It is crucial to distinguish the signs and symptoms of hypoglycemia, which are divided into two categories:

• Confusion, fatigue, headache, drowsiness, coma, and convulsions are some of the signs of neuroglycopenia.
• Autonomic symptoms include tremors, palpitations, nausea, tachycardia, diarrhoea, and anxiety.

STORAGE CONDITIONS:

Maintain room temperature.