Vigamet

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  Indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM who are inadequately controlled on:
• Metformin monotherapy
• Vildagliptin monotherapy
• Dual therapy with metformin and a sulfonylurea
• Dual therapy with metformin and insulin

Combination Therapy Indications:

• Initial combination therapy in adults with severe hyperglycemia not adequately controlled with monotherapy.
• Triple therapy in combination with a sulfonylurea and metformin when dual therapy fails.
• Combination with insulin when diet, exercise, and a stable dose of insulin do not sufficiently control blood glucose.

Clinically Accepted Off-label Use:

• Polycystic Ovary Syndrome (PCOS):
  Used off-label in insulin-resistant PCOS patients as part of a metformin-based regimen.

Available Strengths (verified in Bangladesh):

• Vildagliptin 50 mg + Metformin 500 mg / 850 mg / 1000 mg tablets

Adult Dosage:

• Standard dose:
  Vildagliptin 50 mg twice daily + Metformin 500 mg or 850 mg twice daily
• Maximum dose:
  Vildagliptin 100 mg per day + Metformin 2000 mg per day (in divided doses)
• Administration:
  Oral administration with meals to reduce gastrointestinal side effects

Renal Impairment:

• eGFR ≥ 60 mL/min/1.73 m²: No dose adjustment required
• eGFR 45–59 mL/min/1.73 m²: Use with caution; start at lower metformin dose; monitor renal function
• eGFR < 45 mL/min/1.73 m²: Contraindicated

Hepatic Impairment:

• Not recommended due to the potential risk of lactic acidosis and limited data on vildagliptin in hepatic dysfunction

Geriatric Use:

• Dose should be adjusted based on renal function; regular renal function monitoring is advised

Pediatric Use:

• Not recommended for individuals under 18 years due to lack of safety and efficacy data

Vildagliptin is a selective inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme, which degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By inhibiting DPP-4, vildagliptin increases incretin levels, thereby enhancing glucose-dependent insulin secretion and suppressing glucagon secretion, ultimately lowering blood glucose levels.
Metformin is a biguanide that reduces hepatic glucose production (gluconeogenesis), enhances peripheral glucose uptake, and improves insulin sensitivity, with minimal risk of hypoglycemia as it does not stimulate insulin secretion. The combination addresses both fasting and postprandial hyperglycemia through complementary mechanisms.

Vildagliptin:

• Absorption: Rapid, peak concentration in ~1.7 hours
• Bioavailability: ≥85%
• Distribution: Moderate (Volume of distribution ~71 L)
• Metabolism: Primarily hydrolyzed; minimal CYP involvement
• Half-life: Approximately 3 hours
• Excretion: Mainly renal (~85%); ~23% as unchanged drug

Metformin:

• Absorption: Incomplete (~50–60%); peak plasma levels in 2–3 hours
• Bioavailability: 50–60%
• Distribution: Not bound to plasma proteins
• Metabolism: Not metabolized hepatically
• Half-life: ~6.2 hours
• Excretion: Renal elimination of unchanged drug (90%)

Pregnancy:

• FDA Category (historical): Category B for both agents
• Current guidance: Use only if clearly needed during pregnancy; insulin is the preferred agent when appropriate

Lactation:

• Metformin: Small quantities excreted into breast milk; generally considered safe for breastfeeding
• Vildagliptin: Unknown if excreted in breast milk; caution is advised. Use only if the expected benefit outweighs the potential risk

• Primary Class: Oral Antidiabetic Agents
• Subclasses:
• Vildagliptin: DPP-4 Inhibitor (Incretin Enhancer)
• Metformin: Biguanide Antihyperglycemic

• Hypersensitivity to vildagliptin, metformin, or any component of the formulation
• Moderate to severe renal impairment (eGFR < 45 mL/min/1.73 m²)
• Acute or chronic metabolic acidosis (e.g., diabetic ketoacidosis)
• Hepatic impairment
• Alcohol intoxication or chronic alcohol use
• Conditions associated with hypoxia (e.g., cardiac or respiratory failure)
• Dehydration, severe infection, or shock
• Recent or planned use of iodinated contrast agents (metformin should be withheld)

• Lactic Acidosis: A rare but potentially fatal complication of metformin therapy; monitor renal function closely
• Hepatotoxicity: Liver enzyme elevations reported with vildagliptin; perform periodic liver function tests
• Pancreatitis: Rare cases reported with DPP-4 inhibitors; monitor for persistent abdominal pain
• Hypoglycemia: May occur when combined with insulin or sulfonylureas
• Heart Failure: Use caution in patients with NYHA class I–II heart failure; contraindicated in class III–IV
• Skin Disorders: Rare bullous pemphigoid associated with DPP-4 inhibitors

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, abdominal discomfort, diarrhea (primarily due to metformin)
• Neurological: Headache, dizziness
• Dermatologic: Rash, pruritus

Serious or Rare Side Effects:

• Lactic acidosis (metformin-related)
• Elevated liver enzymes or hepatitis (vildagliptin-related)
• Pancreatitis
• Bullous pemphigoid
• Hypoglycemia (especially with insulin or sulfonylurea co-use)

Dose and Timing Considerations:

• GI side effects are more common during initiation or dose escalation
• Risk of hepatic or skin-related adverse events may increase over time

• Cimetidine: Inhibits renal tubular secretion, increasing metformin levels
• Diuretics, ACE inhibitors, ARBs: May impair renal function, increasing metformin accumulation
• Alcohol: Increases risk of lactic acidosis
• Iodinated contrast agents: Can cause acute renal failure; metformin should be withheld before and after exposure
• Beta-blockers: May mask signs of hypoglycemia
• CYP450 enzymes: Vildagliptin has minimal involvement; no major CYP interactions

• FDA/EMA: Continued monitoring of rare pancreatitis and bullous pemphigoid with DPP-4 inhibitors
• ADA-EASD 2024 Guidelines:
  DPP-4 inhibitors like vildagliptin remain a valid option when SGLT2 inhibitors or GLP-1 receptor agonists are contraindicated or not tolerated
  Metformin remains first-line unless contraindicated
  Renal function monitoring is emphasized, particularly in elderly patients

• Temperature: Store below 25°C
• Humidity: Store in a dry place
• Light: Protect from direct sunlight
• Handling: Do not store in humid areas (e.g., bathroom)
• Freezing: Do not freeze
• Reconstitution: Not applicable (oral tablet form)