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Alogliptin/Pioglitazone Tablets

Alogliptin/pioglitazone is a combination oral antidiabetic medication used to manage type 2 diabetes mellitus. This article explores its pharmacology, clinical applications, and safety profile, referencing authoritative sources including the British National Formulary (BNF)Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology.

Alogliptin: A dipeptidyl peptidase-4 (DPP-4) inhibitor, alogliptin prolongs the action of incretin hormones (GLP-1 and GIP), which enhance glucose-dependent insulin secretion and suppress glucagon release (Lippincott). By inhibiting DPP-4, it increases active incretin levels by 2-3 fold, improving postprandial glycemic control (BNF).

Pioglitazone: A thiazolidinedione (TZD), pioglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-γ), increasing insulin sensitivity in adipose tissue, muscle, and liver. This reduces hepatic glucose output and enhances peripheral glucose uptake (Lange).

Combined Effect: Together, they address both insulin deficiency (alogliptin) and insulin resistance (pioglitazone), offering dual glycemic control (BNF).

  • Primary Indication: Management of type 2 diabetes mellitus in adults inadequately controlled by monotherapy (e.g., metformin) or as initial combination therapy when significant insulin resistance is present (BNF).
  • Adjunctive Therapy: May be combined with other agents (e.g., sulfonylureas, insulin) under specialist guidance (Lange).
  • Available Strengths: Alogliptin (12.5 mg or 25 mg) combined with pioglitazone (15 mg, 30 mg, or 45 mg). Common formulations include 12.5/15, 12.5/30, and 25/15 mg (BNF).
  • Standard Dose: Typically once daily, adjusted based on renal/hepatic function and glycemic response.
    • Renal Impairment: Alogliptin dose reduction (e.g., 12.5 mg daily if eGFR <60 mL/min) (BNF).
    • Pioglitazone: Max 45 mg/day; avoid in hepatic impairment.
  • Alogliptin: Nasopharyngitis, headache, upper respiratory infections.
  • Pioglitazone: Weight gain, edema, musculoskeletal pain.

Serious:

  • Pioglitazone: Heart failure exacerbation, fractures (especially in women), bladder cancer (long-term use), elevated LDL.
  • Alogliptin: Acute pancreatitis (rare), hypersensitivity reactions (Lippincott).

Hypoglycemia: Risk increases with concomitant insulin/sulfonylureas (BNF).

  • Contraindications:
    • Heart failure (NYHA Class III-IV), diabetic ketoacidosis, severe hepatic impairment.
      • History of bladder cancer or hematuria (pioglitazone) (BNF).
    • Renal/hepatic function, HbA1c, weight, edema, and signs of heart failure.
    • Bone density in long-term pioglitazone use (Lange).

Category C (pioglitazone); avoid unless benefits outweigh risks

  • Pioglitazone:
    • CYP2C8 Inhibitors (e.g., gemfibrozil): Increase pioglitazone levels.
    • Oral Contraceptives: Reduced efficacy due to CYP3A4 induction.
  • Alogliptin:
    • Minimal CYP interactions; caution with strong CYP3A4/2D6 inducers (e.g., rifampicin).
  • General: Hypoglycemia risk with sulfonylureas/insulin; avoid concomitant TZDs (Lippincott).
  • Generic: Alogliptin/pioglitazone.

Brand Examples: Incresync® (EU), Oseni® (US).

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