Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-γ), a nuclear receptor predominantly expressed in adipose tissue, muscle, and the liver. This activation leads to:

1. Enhanced Insulin Sensitivity:
   • Promotes adipocyte differentiation and increases adiponectin secretion, improving glucose uptake in muscle and fat (Lippincott).
   • Reduces hepatic glucose production by suppressing gluconeogenesis (Lange).
2. Lipid Metabolism:
   • Lowers triglycerides and increases HDL cholesterol, though it may raise LDL cholesterol marginally (BNF).

1. BNF-Approved Indications:
   • Type 2 Diabetes Mellitus: Monotherapy or combined with metformin, sulfonylureas, or insulin when glycemic targets are unmet.
2. Contraindications:
   • Heart failure (NYHA Class III-IV), history of bladder cancer, diabetic ketoacidosis, severe hepatic impairment (BNF).

• Initial Dose: 15–30 mg once daily, taken with or without food.
• Maintenance: May increase to 45 mg/day after 3–6 months if needed (BNF).
• Adjustments:
  • Hepatic Impairment: Avoid in severe liver disease; monitor LFTs at baseline and periodically.
  • Renal Impairment: No dose adjustment required, but avoid in severe renal dysfunction due to fluid retention risks (Lange).

1. • Weight Gain: Due to fat redistribution and fluid retention.
   • Edema: Risk increases with higher doses or concomitant insulin use (BNF).
   • Fractures: Higher incidence in postmenopausal women (long-term use) (Lippincott).
2. Serious but Rare:
   • Bladder Cancer: Associated with prolonged use (>1 year); monitor for hematuria.
   • Heart Failure: Exacerbates fluid retention, particularly in predisposed patients (BNF).

• Contraindications:
  • History of bladder cancer, active liver disease, or heart failure (BNF).

• • Liver Function Tests: Baseline and periodically. Discontinue if ALT >3x upper limit.
  • Cardiovascular Assessment: Evaluate for heart failure symptoms before and during treatment (Lange).

• Pregnancy:
  • BNF Category: Avoid (limited data; insulin preferred for gestational diabetes).

1. CYP2C8/3A4 Interactions:
   • Inducers (e.g., Rifampicin): Reduce pioglitazone efficacy by accelerating metabolism.
   • Inhibitors (e.g., Gemfibrozil): Increase pioglitazone levels, raising hypoglycemia risk (Lippincott).
2. Insulin/Other Hypoglycemics:
   • Synergistic hypoglycemia risk; monitor glucose levels closely (BNF).
3. NSAIDs:
   • May exacerbate fluid retention and edema (Lange).

• Generic Name: Pioglitazone.
• Brand Names:
  • UK (BNF): Glustin®, Competact® (combined with metformin).
  • US: Actos®, Oseni® (combined with alogliptin).