DIACTIN TABLET

Indications

• Type 2 diabetes mellitus
• Diabetes mellitus management

Dosage

Adults: Initially, 2.5–5 mg daily, adjusted according to response. The dose should be taken shortly before breakfast or lunch, with doses up to 15 mg possibly given as a single dose. Higher doses may be administered in divided doses, with a maximum of 20 mg per day.

Mechanism of action

Glipizide acts as an insulin secretagogue by binding to the sulfonylurea receptor on pancreatic beta-cell membranes. This interaction leads to the closure of ATP-sensitive potassium channels, resulting in membrane depolarization and subsequent calcium influx, which stimulates insulin release. The effectiveness of glipizide is contingent on the presence of functional beta cells in the pancreas.

Pharmacodynamics

Glipizide lowers blood glucose levels, with an onset of action occurring approximately 30 minutes after administration. Its duration of action lasts between 12 to 24 hours. While chronic use does not elevate fasting insulin levels, it enhances the postprandial insulin response. The drug also exerts some extrapancreatic effects, influencing insulin signaling in muscle, fat, and liver cells. However, long-term administration may lead to down-regulation of sulfonylurea receptors, potentially diminishing its efficacy over time.

Pharmacokinetics

Glipizide is absorbed rapidly after oral administration, with peak plasma concentrations typically occurring within 1 to 3 hours. It is mainly metabolized in the liver, and its metabolites are eliminated through urine. The half-life of glipizide is approximately 2 to 4 hours. Factors such as hepatic impairment may require dose adjustments due to altered metabolism.

Contra-indications

• Acute porphyrias
• Hypersensitivity to glipizide or any of its components

Adverse effects

• Hypoglycaemia
• Weight gain
• Gastrointestinal discomfort
• Dizziness
• Headache
• Confusion
• Tremor
• Upper abdominal pain
• Hyponatraemia
• Malaise
• Rare hypersensitivity reactions
• Vasculitis

Interactions

• Other antidiabetic agents
• Beta-blockers
• Thiazide diuretics
• Corticosteroids
• Hormonal contraceptives
• Monoamine oxidase inhibitors
• Anticoagulants

Precautions

• Caution in patients with hepatic impairment
• Monitor for potential hypoglycaemia
• Regular hepatic and haematological monitoring is recommended
• Use with caution in patients with renal impairment

Pregnancy

The use of sulfonylureas in pregnancy should generally be avoided because of the risk of neonatal hypoglycaemia.

Breast-feeding

Avoid due to the theoretical possibility of hypoglycaemia in the infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Glipizide 5 mg tablets
• Glipizide 10 mg tablets
• Glipizide 20 mg tablets

Mechanism of action

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with increasing prevalence worldwide. Characterized by higher-than-normal levels of blood glucose, T2DM is a complex disorder that arises from the interaction between genetic, environmental and behavioral risk factors. Insulin is a peptide hormone that plays a critical role in regulating blood glucose levels. In response to high blood glucose levels, insulin promotes the uptake of glucose into the liver, muscle cells, and fat cells for storage. Although there are multiple events occurring that lead to the pathophysiology of T2DM, the disorder mainly involves insulin insensitivity as a result of insulin resistance, declining insulin production, and eventual failure of beta cells of pancreatic islets that normally produce insulin. Early management with lifestyle intervention, such as controlled diet and exercise, is critical in reducing the risk of long-term secondary complications, such as cardiovascular mortality. Glipizide, like other sulfonylurea drugs, is an insulin secretagogue, which works by stimulating the insulin release from the pancreatic beta cells thereby increasing the plasma concentrations of insulin. Thus, the main therapeutic action of the drug depends on the functional beta cells in the pancreatic islets. Sulfonylureas bind to the sulfonylurea receptor expressed on the pancreatic beta-cell plasma membrane, leading to the closure of the ATP-sensitive potassium channel and reduced potassium conductance. This results in depolarization of the pancreatic beta cell and opening of the voltage-sensitive calcium channels, promoting calcium ion influx. Increased intracellular concentrations of calcium ions in beta cells stimulates the secretion, or exocytosis, of insulin granules from the cells. Apart from this main mechanism of action, the blood-glucose-lowering effect of glipizide involves increased peripheral glucose utilization via stimulating hepatic gluconeogenesis and by increasing the number and sensitivity of insulin receptors.

Pharmacodynamics

Glipizide is a blood glucose-lowering agent. The initial onset of blood glucose-lowering effect occurs around 30 minutes post-administration with the duration of action lasting for about 12 to 24 hours. While the chronic use of glipizide does not result in elevations in the fasting insulin levels over time, the postprandial insulin response, or insulin response to a meal, is observed to be enhanced, even after 6 months of treatment. The main therapeutic actions of glipizide primarily occur at the pancreas where the insulin release is stimulated, but glipizide also mediates some extrapancreatic effects, such as the promotion of insulin signaling effects on the muscles, fat, or liver cells. Due to its action on the endogenous cells, sulfonylureas including glipizide is associated with a risk for developing hypoglycemia and weight gain in patients receiving the drug. Chronic administration of glipizide may result in down-regulation of the sulfonylurea receptors on pancreatic beta cells, which are molecular targets of the drug, leading to a reduced effect on insulin secretion. Like other sulfonylureas, glipizide may work on pancreatic delta (δ) cells and alpha (α) cells to stimulate the secretion of somatostatin and suppress the secretion of glucagon, which are peptide hormones that regulate neuroendocrine and metabolic pathways. Other than its primary action on the pancreas, glipizide also exerts other biological actions outside of the pancreas, or "extrapancreatic effects", which is similar to other members of the sulfonylurea drug class. Glipizide may enhance the glucose uptake into the skeletal muscles and potentiate the action of insulin in the liver. Other effects include inhibited lipolysis in the liver and adipose tissue, inhibited hepatic glucose output, and increased uptake and oxidation of glucose. It has also been demonstrated by several studies that the chronic therapeutic use of sulfonylureas may result in an increase in insulin receptors expressed on monocytes, adipocytes, and erythrocytes.