Pioglitazone

An insulin-sensitizing thiazolidinedione used in type 2 diabetes mellitus.

What is Pioglitazone?

Pioglitazone is a thiazolidinedione (TZD) antidiabetic drug used to improve insulin sensitivity in type 2 diabetes mellitus.

It does not stimulate insulin secretion and has a low risk of hypoglycemia when used alone.

History & Background

Pioglitazone was developed to target insulin resistance by activating nuclear receptors involved in glucose and lipid metabolism.

Chemical Structure & Properties

• IUPAC name: (±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione
• Molecular formula: C₁₉H₂₀N₂O₃S
• Molar mass: 356.44 g/mol
• Functional groups: Thiazolidinedione ring

Mechanism of Action

Pioglitazone lowers blood glucose by:

• Activating PPAR-γ nuclear receptors
• Increasing insulin sensitivity in muscle and adipose tissue
• Reducing hepatic glucose output

Pharmacokinetics

• Absorption: Well absorbed orally
• Peak plasma time: 2 hours
• Metabolism: Liver (CYP2C8, CYP3A4)
• Half-life: 3–7 hours (active metabolites longer)
• Excretion: Bile and feces

Medical Uses

• Type 2 diabetes mellitus
• Insulin resistance
• Combination therapy with metformin or insulin

Dosage Guidelines

Adults: 15–45 mg once daily

Titration: Based on glycemic response

⚠️ Weight gain and fluid retention may occur.

Side Effects

• Weight gain
• Edema
• Fluid retention
• Increased fracture risk (women)

Warnings & Precautions

• Contraindicated in heart failure
• Monitor liver enzymes
• Avoid in active bladder cancer

Drug Interactions

• Insulin (↑ edema risk)
• Gemfibrozil (↑ pioglitazone levels)
• Oral contraceptives

Frequently Asked Questions

Does pioglitazone cause hypoglycemia? – Rare when used alone.

Is it safe long-term? – Yes, with monitoring.

Does it cause weight gain? – Yes.

Can it be combined with metformin? – Yes.

⚠️ Educational content only. Not a substitute for professional medical advice.