Vigatin

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  Vildagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM in the following scenarios:
• As monotherapy in patients who are inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to intolerance or contraindications.
• As dual oral therapy in combination with:
• Metformin, when diet, exercise, and metformin alone do not provide adequate glycemic control.
• A sulfonylurea, when diet, exercise, and sulfonylurea alone do not result in adequate control (usually in patients who cannot tolerate metformin).
• A thiazolidinedione, when diet, exercise, and thiazolidinedione alone fail to provide control.
• Insulin, when stable insulin doses with diet and exercise fail to achieve adequate glycemic control.

Off-label (Clinically Accepted) Use:

• Polycystic Ovary Syndrome (PCOS):
  Occasionally used in combination with metformin in insulin-resistant PCOS patients to enhance glycemic control and reduce androgen excess (experimental or adjunctive use; not FDA-approved).

General Administration:

• Route: Oral
• Tablet Form: Vildagliptin 50 mg
• Timing: With or without food
• Frequency: Once or twice daily, depending on the combination regimen

Monotherapy or Dual Therapy with Metformin or Thiazolidinedione:

• Dose: 50 mg twice daily (morning and evening)

Dual Therapy with a Sulfonylurea:

• Dose: 50 mg once daily (morning), due to increased risk of hypoglycemia when combined with a sulfonylurea

Combination with Insulin:

• Dose: 50 mg twice daily

Maximum Dose:

• 100 mg/day (should not be exceeded)

Special Populations:

• Renal Impairment:
• Mild (eGFR ≥ 60 mL/min): No dose adjustment required
• Moderate to severe (eGFR 30–59 mL/min): 50 mg once daily
• End-stage renal disease (eGFR < 30 mL/min): Use with caution; limited data available
• Hepatic Impairment:
• Moderate to severe impairment: Use not recommended due to potential hepatotoxicity
• Geriatric Use:
• No dose adjustment required based on age alone, but renal function should be monitored regularly
• Pediatric Use:
• Not approved for use in children and adolescents under 18 years of age

Vildagliptin is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 rapidly degrades incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are released postprandially. Inhibition of DPP-4 increases circulating levels of active incretins, which in turn enhance glucose-dependent insulin secretion from pancreatic beta cells and suppress glucagon secretion from alpha cells. These effects reduce hepatic glucose output and improve both fasting and postprandial blood glucose levels, without significantly increasing the risk of hypoglycemia when used as monotherapy.

• Absorption:
  Rapidly absorbed after oral administration; peak plasma concentration (Tmax) occurs within approximately 1.7 hours
• Bioavailability:
  High oral bioavailability (~85%)
• Distribution:
  Volume of distribution is approximately 71 L; minimal binding to plasma proteins (<10%)
• Metabolism:
  Primarily metabolized by hydrolysis to inactive metabolites; does not involve CYP450 enzymes, reducing potential for drug interactions
• Half-life:
  Elimination half-life is approximately 3 hours, but pharmacodynamic effects last longer due to enzyme inhibition
• Elimination:
  Around 85% excreted via urine (23% unchanged); 15% via feces

Pregnancy:

• FDA Classification: Category B (historical); currently no controlled data in pregnant women
• Clinical Guidance: Use only if the potential benefit justifies the potential risk; insulin is preferred during pregnancy for optimal glucose control

Lactation:

• Unknown whether vildagliptin is excreted into human breast milk
• Due to potential risk to the nursing infant, breastfeeding is not recommended while on vildagliptin unless the benefit outweighs the risk

• Primary Therapeutic Class: Oral Antidiabetic Agent
• Subclass: Dipeptidyl Peptidase-4 (DPP-4) Inhibitor
• Also known as an Incretin Enhancer
• Falls under the incretin-based therapies category

• Hypersensitivity to vildagliptin or any component of the formulation
• Patients with moderate to severe hepatic impairment
• Use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis
• History of angioedema related to DPP-4 inhibitors

• Hepatic Monitoring:
  Liver enzyme elevations have been reported; monitor liver function (ALT, AST) before treatment and periodically thereafter
• Pancreatitis Risk:
  Rare cases of acute pancreatitis reported; discontinue if pancreatitis is suspected
• Hypoglycemia:
  Risk increases significantly when used with sulfonylureas or insulin; dose adjustments may be required in such combinations
• Renal Impairment:
  Use with caution; dose adjustment needed in moderate to severe impairment
• Skin Disorders:
  Rare cases of bullous pemphigoid have been reported with DPP-4 inhibitors; if suspected, discontinue vildagliptin
• Heart Failure:
  Although not contraindicated, use caution in patients with NYHA class I–II heart failure; avoid in class III–IV

Common Side Effects:

• Gastrointestinal: Nausea, constipation, dyspepsia
• Neurological: Headache, dizziness
• General: Fatigue, weight-neutral effect

Serious or Rare Adverse Effects:

• Hepatotoxicity: Elevated liver enzymes, rare cases of hepatitis
• Pancreatitis: Rare, serious adverse event; monitor for severe abdominal pain
• Skin Reactions: Rash, urticaria, angioedema, bullous pemphigoid
• Arthralgia or joint pain: Severe joint pain reported in post-marketing experience

Timing & Severity:

• Most common side effects are mild and occur within the first few weeks
• Hepatic effects may develop insidiously and require routine monitoring

• CYP450 Enzyme System:
  Vildagliptin has minimal interaction with the cytochrome P450 system, reducing drug-drug interaction potential
• Combination with Sulfonylureas or Insulin:
  May increase the risk of hypoglycemia; dosage adjustments may be necessary
• ACE Inhibitors (e.g., Lisinopril):
  Concomitant use may increase risk of angioedema, especially in those with a history of hypersensitivity
• Alcohol:
  Should be used cautiously, particularly if combined with agents that may cause hypoglycemia
• Digoxin, Warfarin:
  No significant pharmacokinetic interactions noted

• FDA Safety Communication (Ongoing):
  DPP-4 inhibitors including vildagliptin have been under safety review for pancreatitis and bullous pemphigoid; product labeling has been updated accordingly
• ADA & EASD 2024 Guidelines:
  Vildagliptin remains a second-line agent in patients not controlled on metformin and lifestyle changes
  Preferred in elderly or renal-compromised patients who cannot tolerate SGLT2 inhibitors or GLP-1 receptor agonists
• EMA Recommendations:
  Continued pharmacovigilance on hepatic enzyme monitoring and dermatologic adverse effects

• Storage Temperature: Store below 25°C
• Humidity: Keep in a dry place; avoid exposure to moisture
• Light: Protect from direct sunlight
• Handling: Store in original packaging; do not crush or split tablets
• Reconstitution or Refrigeration: Not applicable (solid oral tablet formulation)
• Other Precautions: Keep out of reach of children; do not use expired medication