pioglitazone

Actions and Spectrum: 

pioglitazone belongs to a class of medications called thiazolidinediones, or glitazones. It works by increasing the body’s sensitivity to insulin, a hormone that helps control blood sugar levels. 

The spectrum of pioglitazone’s action includes: 

• Improving insulin sensitivity: pioglitazone helps the body use insulin more effectively by increasing the number and activity of insulin receptors in the body’s tissues. 
• Reducing glucose production: pioglitazone helps reduce the liver’s production of glucose, which can lead to lower blood sugar levels. 
• Decreasing insulin resistance: pioglitazone helps reduce insulin resistance, which is a major factor in the development of type 2 diabetes. 
• Lowering blood lipid levels: pioglitazone can also help lower levels of triglycerides and increase levels of HDL (good) cholesterol. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined 

>10% 

Upper respiratory infection 

Hypoglycemia 

1-10% 

Headache  

Heart failure  

Sinusitis  

Fracture of bone  

Pharyngitis  

Myalgia  

Frequency not defined 

Nausea 

Diarrhea 

Black Box Warning: 

The warning states that “Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients.

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity to pioglitazone or any of its components 
• Severe heart failure 
• History of bladder cancer 
• Active liver disease or elevated liver enzymes 

Cautions: 

• Mild to moderate heart failure 
• Edema (fluid retention) 
• Macular edema (swelling in the eye) 
• Ovulation may occur in premenopausal anovulatory women, which may result in unintended pregnancy. 

Pregnancy consideration:  

Category B 

Breastfeeding warnings:  

No data is available about the excretion of pioglitazone in breastmilk. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data is available for the drug under this category. 

Pharmacology: 

The pharmacology of pioglitazone includes several mechanisms of action: 

• Activation of PPAR-gamma receptors: pioglitazone binds to peroxisome proliferator-activated receptor gamma (PPAR-gamma) receptors in the nucleus of cells. Activation of these receptors increases insulin sensitivity in adipose tissue, skeletal muscle, and the liver. 
• Inhibition of gluconeogenesis: pioglitazone inhibits glucose production by the liver, which helps to reduce blood sugar levels. 
• Increase in glucose uptake: pioglitazone increases glucose uptake and utilization in adipose tissue and skeletal muscle, which also helps to lower blood sugar levels. 
• Reduction of inflammation: pioglitazone has anti-inflammatory effects that may help to reduce insulin resistance and improve glucose tolerance. 
• Improvement of lipid metabolism: pioglitazone can also improve lipid metabolism by increasing high-density lipoprotein (HDL) cholesterol and reducing low-density lipoprotein (LDL) cholesterol and triglycerides. 

Pharmacodynamics: 

The pharmacodynamics of pioglitazone involves its interactions with peroxisome proliferator-activated receptor gamma (PPAR-gamma) receptors in the nucleus of cells. Once pioglitazone enters the body, it binds to PPAR-gamma receptors and activates them. The activated receptors then trigger a cascade of molecular events that result in several effects on glucose and lipid metabolism. 

pioglitazone’s primary pharmacodynamic effect is the improvement of insulin sensitivity, which leads to increased glucose uptake and utilization in skeletal muscle and adipose tissue. This effect occurs due to the activation of PPAR-gamma receptors in these tissues, resulting in increased expression of insulin-sensitive glucose transporters and enzymes involved in glucose utilization. 

Pharmacokinetics: 

Absorption 

Onset of action takes delayed time 

The duration of action is 24 hours 

The peak plasma concentration is achieved in 2-4 hours (the effect gets delayed with food) 

Distribution 

The protein bound is more than 99% 

The volume of distribution is 0.63 L/kg 

Metabolism 

The drug is metabolized by hepatic CYP3A4 and CYP2C8 and into active metabolites 

Elimination and Excretion 

The half-life is 3-7 hours 

The drug is excreted 15-30% in urine

Administration: 

pioglitazone is usually taken once daily, with or without food. The recommended starting dose of pioglitazone is usually 15 to 30 mg daily, and the maximum dose is 45 mg daily. The dosage may be increased gradually under the guidance of a healthcare professional based on the patient’s response and tolerability. 

pioglitazone should be taken at the same time each day to maintain consistent blood levels of the medication. It should be swallowed whole with a glass of water and should not be crushed, chewed, or broken. 

It is important to follow the dosing instructions provided by the healthcare professional and not to exceed the recommended dose. Taking more pioglitazone than prescribed can increase the risk of side effects. 

pioglitazone can be taken alone or in combination with other medications for diabetes, such as metformin or insulin. If pioglitazone is being used in combination with insulin, the dose of insulin may need to be adjusted to avoid the risk of hypoglycemia. 

If a dose of pioglitazone is missed, it should be taken as soon as possible unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule should be resumed. 

Patient information leaflet 

Generic Name: pioglitazone 

Pronounced: PYE-o-GLIT-a-zone 

Why do we use pioglitazone? 

pioglitazone is used to treat type 2 diabetes, which is a condition where the body is unable to effectively use insulin, resulting in high blood sugar levels. The medication works by improving the body’s sensitivity to insulin, allowing it to better regulate blood sugar levels. 

Pioglitazone is typically prescribed in combination with a healthy diet and regular exercise. It may also be used in combination with other medications such as metformin, sulfonylureas, or insulin. 

Some specific reasons why pioglitazones may be used to treat type 2 diabetes include: 

• Control of blood sugar levels: pioglitazone helps to lower blood sugar levels, which can help to prevent complications associated with uncontrolled diabetes such as kidney damage, nerve damage, and blindness. 
• Improved insulin sensitivity: pioglitazone improves the body’s ability to use insulin, which can help to reduce insulin resistance and improve glucose tolerance. 
• Reduction of cardiovascular risk: pioglitazone has been shown to reduce the risk of heart attack, stroke, and other cardiovascular events in people with type 2 diabetes who have a history of cardiovascular disease. 
• Management of lipid abnormalities: pioglitazone can improve lipid metabolism by increasing HDL cholesterol and reducing LDL cholesterol and triglycerides.