1. Vildagliptin (DPP-4 Inhibitor):
   • Inhibits the enzyme DPP-4, which degrades incretin hormones (GLP-1 and GIP). By prolonging incretin activity, it:
     • Stimulates Glucose-Dependent Insulin Secretion: Enhances β-cell response to hyperglycemia.
     • Suppresses Glucagon Release: Reduces hepatic glucose production (Lippincott).
   • Unlike sulfonylureas, it does not cause hypoglycemia in isolation (Lange).
2. Metformin (Biguanide):
   • Reduces hepatic gluconeogenesis and improves peripheral insulin sensitivity via AMPK activation (BNF).

Synergy: The combination addresses both insulin resistance (metformin) and defective insulin/glucagon secretion (vildagliptin), offering dual-pathway control.

1. BNF-Approved Indications:
   • Vildagliptin Monotherapy: For T2DM when metformin is contraindicated or poorly tolerated.
   • Vildagliptin/Metformin Combination:
     • First-line therapy in patients requiring intensified glycemic control.
     • Adjunct to diet/exercise or other agents (e.g., sulfonylureas, insulin) (BNF).
2. Contraindications:
   • Vildagliptin: Hypersensitivity to DPP-4 inhibitors.
   • Metformin: Severe renal impairment (eGFR <30 mL/min/1.73m²), acidosis, hepatic failure (BNF).

1. Vildagliptin Monotherapy:
   • Adults: 50 mg twice daily, taken with meals (BNF).
   • Renal Adjustment: Avoid if eGFR <50 mL/min/1.73m² (due to limited safety data).
2. Vildagliptin/Metformin Combination:
   • Available Strengths:
     • 50 mg/850 mg
     • 50 mg/1,000 mg
   • Dosing:
     • Initial: 50 mg/500 mg once or twice daily, titrated based on glycemic response.
     • Max Daily Dose: 100 mg vildagliptin + 2,000 mg metformin (BNF).
   • Renal Adjustment:
     • Avoid if eGFR <45 mL/min/1.73m² (metformin component).

1. Vildagliptin:
   • Common: Nasopharyngitis, dizziness, headache.
   • Rare: Pancreatitis, arthralgia, hypersensitivity reactions (BNF).
2. Metformin:
   • Common: GI disturbances (nausea, diarrhea, abdominal pain).
   • Serious: Lactic acidosis (rare but life-threatening; risk factors include renal impairment) (Lippincott).

Combination Therapy: Side effect profile reflects both components, with GI effects predominating.

• Renal Function:
  • Monitor eGFR before and during treatment. Discontinue metformin if eGFR <30 mL/min/1.73m² (BNF).
• Hepatic Impairment: Avoid in severe liver disease (metformin risk).

1. Vildagliptin:
   • ACE Inhibitors (e.g., enalapril): Increased risk of angioedema.
   • Strong CYP3A4 Inducers (e.g., rifampicin): May reduce efficacy (Lippincott).
2. Metformin:
   • Cimetidine: Competes for renal tubular secretion, increasing metformin levels.
   • Iodinated Contrast Media: Temporarily discontinue to prevent lactic acidosis (BNF).

Combination: Interactions reflect both components; monitor glucose levels with concomitant insulin/sulfonylureas.

• • Vildagliptin: Limited data; use only if benefits outweigh risks.
  • Metformin: BNF category not recommended; switch to insulin (Lange).
• Pancreatitis: Discontinue if severe abdominal pain develops (BNF).

• Insulin/Sulfonylureas: Increased hypoglycemia risk; consider dose reduction.
• Oral Medications: Delayed absorption of drugs dependent on rapid GI uptake (e.g., antibiotics, oral contraceptives—take 1 hour before semaglutide).
• Diuretics/NSAIDs: May exacerbate dehydration or renal impairment (Lange).

• Vildagliptin:
  • Generic: Vildagliptin.
  • Brand Names:
    • UK (BNF): Galvus®, Icandra®.
    • Global: Zomelis®.
• Vildagliptin/Metformin:
  • Generic: Vildagliptin + Metformin.
  • Brand Names:
    • UK (BNF): Eucreas®.
    • Global: Galvumet®, Zomarist®.