Usage
- This combination drug is prescribed for the management of type 2 diabetes mellitus in adults when diet and exercise alone do not adequately control blood sugar levels. It is particularly effective in controlling postprandial hyperglycemia (high blood sugar levels after meals).
- Pharmacological Classification: Antidiabetic agent, specifically a combination of a sulfonylurea (gliclazide), a biguanide (metformin), and an alpha-glucosidase inhibitor (voglibose).
- Mechanism of Action: This triple-drug therapy addresses multiple aspects of glucose metabolism. Gliclazide stimulates insulin release from the pancreas. Metformin reduces hepatic glucose production, improves insulin sensitivity, and decreases intestinal glucose absorption. Voglibose delays carbohydrate digestion and absorption in the intestines, reducing post-meal blood sugar spikes.
Alternate Names
- No widely recognized alternate generic names exist.
- Brand Names: Several brand names are available, including Glizid MV, Voglitrio, and Cyblex MV, among others. Availability varies depending on the region.
How It Works
- Pharmacodynamics: Gliclazide increases insulin secretion. Metformin decreases hepatic glucose production and increases peripheral insulin sensitivity. Voglibose inhibits alpha-glucosidase in the small intestine, delaying carbohydrate hydrolysis and glucose absorption, thus reducing postprandial hyperglycemia.
- Pharmacokinetics:
- Gliclazide: Well-absorbed orally, metabolized in the liver, and primarily excreted renally.
- Metformin: Absorbed from the small intestine, not metabolized, and excreted unchanged in the urine.
- Voglibose: Minimally absorbed, with most of the drug acting locally in the intestines. Excreted primarily in feces, with a small fraction excreted in the urine.
- Mode of Action:
- Gliclazide: Binds to sulfonylurea receptors on pancreatic beta cells, closing ATP-sensitive potassium channels, leading to membrane depolarization, calcium influx, and insulin release.
- Metformin: Multiple mechanisms, including activation of AMP-activated protein kinase (AMPK), inhibition of gluconeogenesis, and increased peripheral glucose uptake.
- Voglibose: Competitively inhibits alpha-glucosidase enzymes in the brush border of the small intestine, preventing the breakdown of complex carbohydrates into absorbable monosaccharides.
- Elimination Pathways: Gliclazide is primarily eliminated renally after hepatic metabolism. Metformin is excreted renally unchanged. Voglibose is primarily eliminated fecally, with minimal renal excretion.
Dosage
Standard Dosage
Adults:
- Dosage is individualized based on patient response and blood glucose levels. A common starting dose is one tablet containing Gliclazide 80 mg + Metformin 500 mg + Voglibose 0.2 or 0.3 mg, taken two to three times daily with meals. The maximum dose is based on the individual components and should not exceed the recommended daily limits for each.
Children:
- Not recommended for use in children. Safety and efficacy have not been established in pediatric populations.
Special Cases:
- Elderly Patients: Initiate therapy with a lower dose and titrate cautiously due to increased risk of hypoglycemia and potential age-related decline in renal function. Closely monitor renal function.
- Patients with Renal Impairment: Contraindicated in moderate to severe renal impairment. Use with caution and dose adjustment in mild renal impairment.
- Patients with Hepatic Dysfunction: Use with caution and monitor liver function. Dose adjustment may be necessary.
- Patients with Comorbid Conditions: Consider potential drug interactions and adjust dosage accordingly. Close monitoring is essential, particularly in patients with cardiovascular disease, gastrointestinal disorders, or other chronic illnesses.
Clinical Use Cases
- This combination is specifically indicated for the chronic management of type 2 diabetes mellitus and is not typically used in acute medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Insulin is usually preferred in such cases.
Dosage Adjustments
- Dosage adjustments should be made based on patient response, blood glucose monitoring, and renal/hepatic function. Genetic polymorphisms affecting drug metabolism may also influence dosage requirements.
Side Effects
Common Side Effects
- Hypoglycemia (dizziness, sweating, palpitations, hunger, confusion)
- Gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal pain, flatulence)
- Skin rash
- Altered taste sensation
Rare but Serious Side Effects
- Lactic acidosis (especially in patients with renal impairment)
- Severe hypoglycemia
- Hepatic dysfunction
- Anemia
Long-Term Effects
- Vitamin B12 deficiency (with prolonged metformin use)
- Potential for weight gain
Adverse Drug Reactions (ADR)
- Lactic acidosis
- Severe hypoglycemia
- Angioedema
Contraindications
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal or hepatic impairment
- Congestive heart failure
- Hypersensitivity to any component of the drug
Drug Interactions
- Alcohol (increased risk of hypoglycemia and lactic acidosis)
- Medications that affect renal function (increased risk of metformin accumulation)
- Sulfonylureas, insulin, or other antidiabetic agents (increased risk of hypoglycemia)
- Corticosteroids, thiazide diuretics (may increase blood glucose levels)
- Beta-blockers (may mask symptoms of hypoglycemia)
- CYP450 enzyme inducers/inhibitors (may alter the metabolism of gliclazide)
Pregnancy and Breastfeeding
- Consult a doctor before use during pregnancy and breastfeeding. The safety and efficacy of this combination during pregnancy and lactation have not been fully established. Gliclazide is generally contraindicated during breastfeeding. Metformin may be excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Multifactorial antidiabetic action through insulin secretion stimulation, reduced hepatic glucose production, improved insulin sensitivity, and delayed carbohydrate absorption.
- Side Effects: Hypoglycemia, gastrointestinal issues, skin rash, altered taste.
- Contraindications: Type 1 diabetes, diabetic ketoacidosis, severe renal/hepatic impairment, congestive heart failure, hypersensitivity.
- Drug Interactions: Alcohol, medications affecting renal function, other antidiabetic agents, corticosteroids, beta-blockers, CYP450 inducers/inhibitors.
- Pregnancy & Breastfeeding: Consult doctor before use.
- Dosage: Individualized based on patient response and blood glucose levels, typically starting with one tablet two to three times daily with meals.
- Monitoring Parameters: Blood glucose levels (fasting and postprandial), HbA1c, renal function, liver function, vitamin B12 levels.
Popular Combinations
This medication is already a combination of three drugs. Adding further medications may increase the risk of adverse effects and interactions. However, other antidiabetic agents like DPP-4 inhibitors or GLP-1 receptor agonists may be considered if adequate glycemic control is not achieved with this combination. Any additions should be made under strict medical supervision with careful monitoring.
Precautions
- General Precautions: Assess renal and hepatic function before initiating therapy and periodically during treatment. Monitor blood glucose regularly. Adjust dosage based on blood glucose control. Screen for allergies and contraindications.
- Specific Populations: (See “Dosage - Special Cases” and “Pregnancy and Breastfeeding” sections).
- Lifestyle Considerations: Advise patients on a healthy diet, regular exercise, weight management, and limiting alcohol intake. Caution about the potential for hypoglycemia, especially during exercise or with skipped meals.
FAQs (Frequently Asked Questions)
A: The dosage is individualized based on patient response and blood glucose levels. A common starting dose is one tablet two to three times daily with meals. Dosage adjustments are made based on regular blood glucose monitoring and clinical assessment.
Q2: What are the most common side effects?
A: The most common side effects are hypoglycemia and gastrointestinal issues like nausea, vomiting, diarrhea, and flatulence.
Q3: Who should not take this medication?
A: This medication is contraindicated in patients with type 1 diabetes, diabetic ketoacidosis, severe renal/hepatic impairment, congestive heart failure, and hypersensitivity to any component of the drug.
Q4: How does this combination drug work?
A: It works by improving insulin secretion, reducing hepatic glucose production, enhancing insulin sensitivity, and delaying carbohydrate absorption, thereby controlling blood glucose levels.
Q5: Can this medication be taken during pregnancy or breastfeeding?
A: Consult a doctor before use during pregnancy or breastfeeding. Safety and efficacy during these periods have not been definitively established.
Q6: Are there any drug interactions I should be aware of?
A: Yes, several drug interactions can occur. Inform your doctor about all medications, including over-the-counter drugs and supplements you are taking. Alcohol should be limited due to increased risks of hypoglycemia and lactic acidosis.
Q7: What should I do if I miss a dose?
A: If you miss a dose, take it as soon as you remember. If it is near the time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.
Q8: What are the signs of hypoglycemia, and what should I do if they occur?
A: Signs of hypoglycemia include dizziness, sweating, palpitations, hunger, confusion, and shakiness. If these occur, consume a fast-acting carbohydrate source like glucose tablets or fruit juice, and contact your doctor if symptoms persist or worsen.
Q9: How often should I monitor my blood sugar levels while taking this medication?
A: Your doctor will advise you on how frequently to monitor your blood sugar levels based on your individual needs and treatment response. Regular monitoring is essential for optimizing dosage and preventing complications.
