gliclazide/metformin/pioglitazone

Action and Spectrum

Actions and Spectrum: 

Action: 

gliclazide 

gliclazide is categorized within the sulfonylurea drug class, functioning to promote increased insulin secretion by the pancreas. This helps lower blood sugar levels by increasing the amount of insulin available to move glucose into cells for energy. 

metformin 

metformin is a biguanide medication. It reduces glucose production in the liver, increases insulin sensitivity in muscle cells, and decreases sugar absorption in the intestines. It does not increase insulin production from the pancreas. 

pioglitazone: 

pioglitazone is a thiazolidinedione (TZD) medication. It improves insulin sensitivity in the body’s cells, especially in muscle and fat tissues. It also diminishes hepatic glucose production. 

Spectrum 

gliclazide 

gliclazide primarily works to lower post-meal blood sugar levels. It is effective in managing diabetes when combined with dietary and lifestyle changes. 

metformin 

metformin is used to manage both fasting and post-meal blood sugar levels. It is frequently regarded as an initial therapeutic approach for managing type 2 diabetes and may be employed either as a standalone treatment or in conjunction with other pharmaceuticals. 

pioglitazone 

pioglitazone helps improve insulin resistance, effectively managing fasting and post-meal blood sugar levels. It is often used as an adjunct therapy with other antidiabetic medications. 

Drug Interaction

Adverse Reaction

Frequency not defined  

Stomach pain 

Decreased heartbeat 

Sweating 

Weakness 

Confusion 

Nausea  

Dizziness 

vomiting 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Do not use any of these medications if you have a known hypersensitivity or allergy to gliclazide, metformin, pioglitazone, or any of their components. 

Renal Impairment: Avoid these medications or use with extreme caution if you have severe kidney impairment or end-stage renal disease, as they may require dose adjustments or alternative treatments. 

Hepatic Impairment: Individuals with severe liver disease should avoid these medications or use them with caution, as they can affect liver function and may require dosage adjustments. 

Diabetic Ketoacidosis: These medications should not be used in cases of diabetic ketoacidosis (a life-threatening condition in diabetes), as they are not effective in treating this condition. 

Alcohol Abuse: Excessive alcohol consumption can interact with these medications and increase the risk of lactic acidosis, a potentially life-threatening condition associated with metformin use. 

Pregnancy and Breastfeeding: These medications may not be suitable during pregnancy or breastfeeding, and their use should be carefully considered with a healthcare provider’s guidance. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted 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. 

<b>Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus 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 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

Pharmacology:

gliclazide, metformin, and pioglitazone are medications used to treat type 2 diabetes mellitus. 

Pharmacodynamics:  

gliclazide 

gliclazide belongs to the sulfonylurea class of drugs. It functions by triggering the secretion of insulin from the beta cells in the pancreas. This increased insulin secretion helps lower blood glucose levels. 

metformin 

metformin is a biguanide that primarily decreases hepatic glucose production (gluconeogenesis) and increases insulin sensitivity in peripheral tissues, such as muscle and fat.  

pioglitazone 

pioglitazone is a thiazolidinedione that primarily acts by improving insulin sensitivity in peripheral tissues. It activates peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in adipose tissue, which leads to enhanced glucose uptake and utilization in muscle and fat cells. 

Pharmacokinetics: 

Absorption 

gliclazide undergoes rapid absorption from the gastrointestinal tract following oral ingestion. Food does not significantly affect its absorption, but it is generally recommended to take it with meals to minimize the risk of hypoglycemia. 

metformin is well absorbed from the gastrointestinal tract, with most of the absorption occurring in the small intestine. Food does not influence its absorption but can be slowed by extended-release formulations. 

pioglitazone is also well absorbed from the gastrointestinal tract and can be taken with or without food. Food does not significantly affect its absorption. 

Distribution 

gliclazide is primarily bound to plasma proteins, mainly albumin. Its relatively limited distribution volume suggests that it is primarily contained within the bloodstream. 

metformin is not extensively bound to plasma proteins and has a relatively small distribution volume, meaning it remains mainly in the bloodstream. 

pioglitazone is extensively bound to plasma proteins, mainly to serum albumin. It also has a large volume of distribution, indicating that it can distribute to various tissues in the body. 

Metabolism 

gliclazide is primarily metabolized in the liver through oxidation and conjugation processes. The metabolites are then excreted in the urine. 

metformin is not significantly metabolized in the liver. It is eliminated unchanged in the urine and does not undergo significant hepatic metabolism. 

pioglitazone is extensively metabolized in the liver through cytochrome P450 enzymes, mainly CYP2C8 and CYP3A4. The primary metabolites are excreted in the urine and feces. 

Excretion and Elimination 

gliclazide and its metabolites are primarily excreted in the urine. 

metformin is mainly eliminated through the urinary system without undergoing significant alteration. It is not significantl eliminated through the feces. 

pioglitazone and its metabolic byproducts are mainly eliminated through urinary excretion, with a smaller fraction being excreted in the fecal matter. 

Adminstartion

Administration:  

The route of administration is oral. The healthcare provider will decide the combination and amounts, considering the patient’s individual medical history and reaction to therapy. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: gliclazide/metformin/pioglitazone 

Why do we use gliclazide/metformin/pioglitazone?  

gliclazide, metformin, and pioglitazone can be prescribed together as a triple combination therapy for individuals with type 2 diabetes who have not achieved adequate blood sugar control with monotherapy (single-drug treatment). This combination can be effective in improving glycemic control by targeting multiple aspects of glucose metabolism.  

This combination is particularly useful for individuals with poorly controlled blood sugar levels. metformin helps lower fasting blood glucose levels, while gliclazide and pioglitazone help control post-meal spikes in blood sugar.  

The combination of gliclazide, metformin, and pioglitazone is often prescribed based on individual patient characteristics, including their response to each medication and their specific diabetes-related health needs. It allows healthcare providers to tailor treatment to the unique requirements of the patient.