Usage
- This combination drug is prescribed for the treatment of Type 2 Diabetes Mellitus in adults when diet, exercise, and treatment with single or dual therapy (e.g., Metformin alone or Glimepiride + Metformin) do not provide adequate glycemic control. It is specifically indicated for improving both fasting and postprandial (after-meal) blood glucose levels.
- Pharmacological Classification: Antidiabetic combination, comprising a Sulfonylurea (Glimepiride), a Biguanide (Metformin), and an Alpha-glucosidase inhibitor (Voglibose).
- Mechanism of Action: This triple combination addresses different aspects of glucose regulation: Glimepiride stimulates insulin release from the pancreas; Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and increases insulin sensitivity; and Voglibose delays the digestion and absorption of carbohydrates in the intestine, preventing postprandial glucose spikes.
Alternate Names
- This combination therapy, being a fixed-dose combination (FDC) of three generic drugs, doesn’t have a unique international nonproprietary name (INN). It’s generally referred to by the names of its components: Glimepiride + Metformin + Voglibose.
- Brand Names: This FDC is marketed under various brand names such as Glimisave MV, Glyree MV, Voglimac GM2, Trivoglitor, Trimetride, Xilia Trio, Vogli GM2, Glisen VM, Voglibite GM, Metasens VG, Glucoryl MV, Amaryl MV, Gluconorm VG, Voglinorm GM, Glyciphage VG, Genericart, and others.
How It Works
- Pharmacodynamics: Glimepiride acts on pancreatic beta-cells, binding to sulfonylurea receptors and closing ATP-sensitive potassium channels, causing depolarization and leading to insulin release. Metformin inhibits hepatic gluconeogenesis, enhances peripheral glucose uptake, and reduces intestinal glucose absorption. Voglibose competitively and reversibly inhibits alpha-glucosidase enzymes in the small intestine, delaying the breakdown of complex carbohydrates into glucose.
- Pharmacokinetics: Glimepiride is completely absorbed orally, with a peak plasma concentration within 2-3 hours. It is metabolized in the liver by CYP2C9 and eliminated through renal and biliary routes. Metformin is absorbed slowly and incompletely, reaching peak levels in 2.5 hours (immediate-release) or 7 hours (extended-release). It is minimally metabolized and excreted unchanged by the kidneys. Voglibose is poorly absorbed (less than 2%), with peak plasma levels of metabolites occurring within 1-2 hours. It is metabolized by intestinal bacteria and excreted mainly in feces, with negligible renal excretion.
- Mode of Action (Cellular/Molecular): Glimepiride: Binds to sulfonylurea receptors (SUR1) on pancreatic beta-cells, leading to closure of ATP-sensitive potassium channels. Metformin: Activates AMP-activated protein kinase (AMPK), suppressing hepatic gluconeogenesis and improving peripheral insulin sensitivity. Voglibose: Inhibits alpha-glucosidase enzymes (glucoamylase, sucrase, maltase, and isomaltase) in the small intestinal brush border.
- Elimination Pathways: Glimepiride: Hepatic metabolism (CYP2C9) and renal/biliary excretion. Metformin: Primarily renal excretion. Voglibose: Metabolism by intestinal bacteria and fecal excretion.
Dosage
Standard Dosage
Adults:
- Initial: Glimepiride 1 mg + Metformin 500 mg + Voglibose 0.2 mg once daily with a full meal.
- Titration: Based on glycemic control, the dosage can be gradually increased to a maximum of Glimepiride 4 mg, Metformin 2000 mg, and Voglibose 0.3 mg. The dosage of each component is usually titrated up in combination. For instance, a subsequent step-up might be Glimepiride 2 mg + Metformin 500 mg + Voglibose 0.2 mg.
- Frequency: Once or twice daily, with the total maximum daily dose not exceeding the limits for each individual component.
Children:
- Not recommended for patients under 18 years of age. Safety and efficacy have not been established in pediatric populations.
Special Cases:
- Elderly Patients: Start with a low dose and titrate cautiously due to potential age-related decline in renal function. Close monitoring is essential.
- Patients with Renal Impairment: Use with caution; metformin is contraindicated in moderate to severe renal impairment (eGFR < 30 ml/min). Glimepiride dosage adjustment may be needed.
- Patients with Hepatic Dysfunction: Use with caution; metformin is not recommended in hepatic impairment. Glimepiride dosage adjustment may be necessary.
- Patients with Comorbid Conditions: Carefully consider in patients with cardiovascular disease, vitamin B12 deficiency, or other conditions that may be affected by the individual components.
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations: This specific FDC is not generally indicated for use in these settings. Insulin therapy is usually preferred for acute management of blood glucose in these situations.
Dosage Adjustments
- Dosage adjustments should be individualized based on the patient’s glycemic response, renal function, hepatic function, and other comorbidities. Close monitoring of blood glucose, HbA1c, renal function (eGFR), and hepatic function tests is necessary.
Side Effects
Common Side Effects
- Hypoglycemia (especially with Glimepiride)
- Nausea, diarrhea, stomach pain, flatulence (primarily with Metformin and Voglibose)
- Headache, taste disturbance, upper respiratory tract infections
Rare but Serious Side Effects
- Lactic acidosis (with Metformin)
- Severe hypoglycemia requiring hospitalization
- Allergic reactions (skin rash, itching, angioedema)
- Hemolytic anemia (with Glimepiride)
Long-Term Effects
- Vitamin B12 deficiency (with Metformin)
- Weight gain
Adverse Drug Reactions (ADR)
- Lactic acidosis
- Severe hypoglycemia
- Stevens-Johnson syndrome
Contraindications
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Moderate to severe renal impairment (eGFR < 30 ml/min)
- Severe hepatic dysfunction
- Hypersensitivity to any of the components
- Congestive heart failure requiring pharmacologic treatment
- Chronic metabolic acidosis
- Gastrointestinal obstruction
Drug Interactions
- Alcohol (increases risk of lactic acidosis and hypoglycemia)
- Cationic drugs (compete with Metformin for renal excretion)
- Miconazole, Phenylbutazone (increase hypoglycemic effects of Glimepiride)
- Furosemide (affects pharmacokinetics of both Metformin and Furosemide)
- CYP2C9 inhibitors/inducers (affect Glimepiride metabolism)
- Colesevelam (reduces Glimepiride absorption)
- Beta-blockers, other antidiabetic drugs (increase risk of hypoglycemia)
Pregnancy and Breastfeeding
- Pregnancy: Not recommended. Insulin is typically preferred for managing blood glucose during pregnancy.
- Breastfeeding: Not recommended. Metformin is excreted in breast milk and Glimepiride is potentially harmful to infants.
Drug Profile Summary
- Mechanism of Action: See above.
- Side Effects: See above.
- Contraindications: See above.
- Drug Interactions: See above.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: See above.
- Monitoring Parameters: Blood glucose, HbA1c, renal function tests (eGFR, creatinine), liver function tests, vitamin B12 levels.
Popular Combinations
- This combination itself is a popular choice when dual therapy is insufficient.
- It is often used in conjunction with other antidiabetic agents like DPP-4 inhibitors or SGLT2 inhibitors if further glycemic control is needed.
Precautions
- General Precautions: Careful patient selection, baseline assessment of renal and hepatic function, monitoring for hypoglycemia and other side effects.
- Specific Populations: See “Special Cases” under Dosage.
- Lifestyle Considerations: Emphasis on diet, exercise, and weight management is crucial. Alcohol should be avoided or consumed in moderation.
FAQs (Frequently Asked Questions)
A: The initial dosage is typically Glimepiride 1mg + Metformin 500mg + Voglibose 0.2mg once daily with a meal. Titration up to maximum doses of each component should be based on the patient’s glycemic response and tolerability.
Q2: What are the common side effects?
A: Common side effects include hypoglycemia, gastrointestinal issues (nausea, diarrhea, flatulence), headache, and taste changes.
Q3: Is this combination safe for patients with kidney disease?
A: It should be used cautiously in patients with mild renal impairment and is contraindicated in moderate to severe renal dysfunction. Metformin is primarily excreted by the kidneys and can accumulate in patients with reduced kidney function, increasing the risk of lactic acidosis.
Q4: Can it be used during pregnancy or breastfeeding?
A: It is generally not recommended during pregnancy or while breastfeeding. Insulin is usually the preferred treatment for diabetes during pregnancy.
Q5: What are the major drug interactions to be aware of?
A: Significant interactions can occur with alcohol, cationic drugs, miconazole, CYP2C9 inhibitors/inducers, and colesevelam.
Q6: What should I monitor in patients taking this combination?
A: Closely monitor blood glucose, HbA1c levels, renal function (eGFR, creatinine), liver function tests, and Vitamin B12 levels.
Q7: When is this combination prescribed?
A: This triple drug combination is considered when blood glucose is inadequately controlled with diet, exercise, and single or dual therapy with other antidiabetic agents.
Q8: What are the contraindications for using this drug?
A: The drug is contraindicated in patients with type 1 diabetes, diabetic ketoacidosis, severe renal or hepatic impairment, hypersensitivity to its components, and certain other conditions.
Q9: How does Voglibose contribute to the overall efficacy of this combination?
A: Voglibose targets postprandial hyperglycemia by delaying carbohydrate absorption, which complements the actions of Glimepiride and Metformin in controlling both fasting and postprandial glucose levels.
