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).