Vildagliptin

Vildagliptin is an oral DPP-4 inhibitor taken twice daily, or once daily with a sulphonylurea. It lowers HbA1c by about 0.5 to 1% and has low hypoglycaemia risk. It is widely used across Africa, Asia and Europe, is not licensed in the United States, and needs liver enzyme monitoring.

Classification. DPP-4 inhibitor (gliptin), cyanopyrrolidine. Tablets 50 mg; fixed-dose combinations with metformin.

Mechanism. Binds DPP-4 covalently and reversibly, raising active GLP-1 and GIP and so increasing glucose-dependent insulin release and suppressing glucagon.

Pharmacodynamics. Over 90% DPP-4 inhibition at peak with 50 mg twice daily, and about 50% or more is maintained over 12 hours after a dose, which explains twice-daily dosing.

Pharmacokinetics. Bioavailability about 85%; peak 1 to 2 hours; low protein binding. About 69% is cleared by hydrolysis to an inactive metabolite, with minimal CYP involvement. About 85% appears in urine, one third as unchanged drug. Half-life about 2 to 3 hours, with DPP-4 inhibition lasting longer.

Type 2 diabetes, adults.

• With metformin, pioglitazone, insulin or alone: 50 mg orally twice daily (morning and evening), with or without food.
• With a sulphonylurea: 50 mg once daily in the morning; a higher dose gives more hypoglycaemia without more benefit.
• Maximum 100 mg daily. No loading dose.
• Continue long term if HbA1c falls by at least 0.5% within 6 months; otherwise stop.

Combination use. Adds to metformin, sulphonylureas, pioglitazone, SGLT2 inhibitors and insulin. Reduce the sulphonylurea or insulin dose when adding it. Do not combine with a GLP-1 receptor agonist or another DPP-4 inhibitor.

Adjustments.

• Kidney: no change when eGFR is 50 mL/min/1.73 m2 or more; 50 mg once daily when eGFR is under 50, including dialysis.
• Liver: do not use in hepatic impairment or when ALT or AST is more than 3 times the upper limit of normal.
• Older adults: dose by eGFR.
• Weight: no weight-based dosing.
• Children: not licensed.

Contraindications. Hypersensitivity to vildagliptin; hepatic impairment including ALT or AST over 3 times the upper limit of normal before treatment; type 1 diabetes; diabetic ketoacidosis.

Serious adverse effects.

• Raised transaminases, rarely hepatitis: stop if ALT or AST stays over 3 times the upper limit of normal, and do not restart.
• Acute pancreatitis: stop if suspected and do not restart if confirmed.
• Angioedema, higher with ACE inhibitors.
• Bullous pemphigoid and exfoliative skin lesions: stop and refer.
• Heart failure: no experience in NYHA class IV and limited in class III; not advised in these patients.

Common adverse effects. Headache, dizziness, tremor; hypoglycaemia mostly with sulphonylureas.

Major interactions.

• Sulphonylureas and insulin: more hypoglycaemia.
• ACE inhibitors: higher angioedema risk.
• Few pharmacokinetic interactions; no meaningful CYP effects.

Special groups.

• Pregnancy: avoid; use insulin.
• Breastfeeding: avoid.
• Older adults: dose by eGFR; useful with low hypoglycaemia risk.
• Kidney impairment: 50 mg once daily when eGFR is under 50.
• Liver impairment: not advised.
• East Africa: relatively available and affordable among gliptins. Studies in people fasting during Ramadan show less hypoglycaemia than with sulphonylureas.

Administration. Twice daily at similar times, with or without food. Swallow whole.

Baseline. HbA1c, eGFR, ALT and AST (required), history of pancreatitis, assessment for heart failure.

Monitoring.

• Liver tests every 3 months in the first year, then periodically.
• HbA1c at 3 and 6 months, then every 6 months.
• eGFR at least annually; adjust the dose when it falls under 50.
• Ask about abdominal pain, blisters and joint pain.

Stopping thresholds. Stop with ALT or AST persistently over 3 times the upper limit of normal, jaundice, suspected pancreatitis, angioedema, bullous pemphigoid, or HbA1c reduction under 0.5% after 6 months.

Referral and escalation. Admit suspected pancreatitis, angioedema or acute liver injury. Refer blistering eruptions to dermatology.