Adult: Vildagliptin 50 mg and metformin 500 mg tab Vildagliptin 50 mg and metformin 850 mg tab Vildagliptin 50 mg and metformin 1,000 mg tab
As an adjunct to diet and exercise: 1 tab bid. Dose is individualised based on the patient's current regimen, tolerability, and response. Max: Vildagliptin 100 mg daily. Treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal Impairment
GFR <30 mL/min: Contraindicated. GFR 30-44 mL/min: Max: Vildagliptin 50 mg and metformin 1,000 mg daily. Initial metformin dose should not exceed half of the Max metformin dose. GFR 45-59 mL/min: Max: Vildagliptin 50 mg and metformin 2,000 mg daily. Initial metformin dose should not exceed half of the Max metformin dose.
Hepatic Impairment
Contraindicated.
Administration
Should be taken with food. Take w/ or immediately after meals to reduce GI discomfort.
Contraindications
Acute or chronic disease that may cause hypoxia (e.g. cardiac or respiratory failure, recent MI), acute or chronic metabolic acidosis (e.g. lactic acidosis or diabetic ketoacidosis with or without coma), diabetic pre-coma, acute conditions that may alter renal function (e.g. dehydration, severe infection, shock, intravascular administration of iodinated contrast agents), acute alcohol intoxication, alcoholism. Hepatic and severe renal (GFR <30 mL/min) impairment. Lactation.
Special Precautions
Patient with history of pancreatitis. Not intended for use in patients with type 1 diabetes mellitus. Patient exposed to stress (e.g. fever, trauma, infection). Discontinue treatment at the time of surgery under general, spinal, or epidural anaesthesia; may restart treatment no earlier than 48 hours after surgery or resumption of oral nutrition and once renal function is stable. Mild to moderate renal impairment. Elderly. Pregnancy.
Adverse Reactions
Significant: Acute pancreatitis, hypoglycaemia, bullous pemphigoid, severe and disabling arthralgia; decreased vitamin B12 levels (long-term use). Rarely, hepatic dysfunction (e.g. hepatitis), exfoliative skin lesions. Gastrointestinal disorders: Nausea, abdominal pain, vomiting, diarrhoea. General disorders and administration site conditions: Fatigue, asthenia. Nervous system disorders: Dizziness, headache, tremor. Skin and subcutaneous tissue disorders: Hyperhidrosis. Rarely, angioedema. Potentially Fatal: Rarely, lactic acidosis.
Monitoring Parameters
Monitor plasma glucose (frequency depends on individual treatment regimen, hypoglycaemia risk, and other patient-specific factors) and HbA1c (at least twice yearly in patients with stable glycaemic control and meeting treatment goals; quarterly for patients not meeting the treatment goals or with change in treatment); LFTs (prior to initiation, during treatment at 3-month intervals during the 1st year and periodically thereafter); renal function (before treatment and regularly thereafter); haematologic parameters such as Hb/haematocrit and RBC indices (annually); vitamin B12 levels (every 1-2 years, particularly in predisposed patients). Monitor for signs and symptoms of pancreatitis and skin disorders (e.g. blistering or ulceration).
Overdosage
Symptoms: Vildagliptin: Muscle pain, mild and transient paraesthesia, fever, oedema, transient increase in lipase levels, increased creatine phosphokinase, AST, C-reactive protein, and myoglobin levels. Metformin: Lactic acidosis. Management: Supportive treatment. May perform haemodialysis to remove metformin and the major metabolite of vildagliptin (LAY151).
Drug Interactions
May decrease hypoglycaemic effect with thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, Ca channel blockers, sympathomimetics, and isoniazid.
Vildagliptin: May increase the risk of hypoglycaemia with sulfonylureas. Increased risk of angioedema with ACE inhibitors.
Metformin: May increase the risk of lactic acidosis with drugs that can adversely affect renal function (e.g. NSAIDs, ARBs, ACE inhibitors, diuretics). Organic cationic transporter-2 (OCT2)/multidrug and toxin extrusion (MATE) inhibitors (e.g. cimetidine, ranolazine, vandetanib, dolutegravir) may increase systemic exposure to metformin. Potentially Fatal: Metformin: Intravascular administration of iodinated contrast agents may cause nephropathy, resulting in increased metformin levels and increased risk of lactic acidosis.
Food Interaction
Metformin: Decreased extent and slightly delayed absorption with food. Increased risk of lactic acidosis with alcohol.
Action
Description: Mechanism of Action: Vildagliptin inhibits dipeptidyl peptidase-4 (DPP4), an enzyme that degrades incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This results in increased fasting and postprandial endogenous levels of GLP-1 and GIP, which enhances the sensitivity of β-cells to glucose resulting in improved glucose-dependent insulin secretion.
Metformin is a biguanide antidiabetic agent that lowers hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, enhances peripheral glucose uptake and utilisation by increasing insulin sensitivity, and delays intestinal absorption of glucose. Pharmacokinetics: Absorption: Vildagliptin: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 85%. Time to peak plasma concentration: 1.75 hours (fasted state); 2.5 hours (with food).
Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Food reduces the extent and slightly delays absorption. Absolute bioavailability: 50-60% (fasting state). Time to peak plasma concentration: 2-3 hours. Distribution: Vildagliptin: Distributed equally between plasma and RBCs. Plasma protein binding: 9.3%.
Metformin: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 63-276 L. Metabolism: Vildagliptin: Metabolised in the kidney (approx 69%) mainly via hydrolysis into the major metabolite LAY151 (inactive). Excretion: Vildagliptin: Via urine (approx 85%; 23% as unchanged drug); faeces (15%). Elimination half-life: Approx 3 hours.
Metformin: Via urine (approx 90% as unchanged drug). Elimination half-life: 4-9 hours (plasma); approx 17.6 hours (blood).
Chemical Structure
Vildagliptin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6918537, Vildagliptin. https://pubchem.ncbi.nlm.nih.gov/compound/Vildagliptin. Accessed Oct. 25, 2023.
Metformin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4091, Metformin. https://pubchem.ncbi.nlm.nih.gov/compound/Metformin. Accessed Feb. 27, 2023.
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