Usage
- Metformin + Voglibose is prescribed for the treatment of Type 2 Diabetes Mellitus, particularly in cases where diet and exercise alone or metformin monotherapy do not provide adequate glycemic control, especially postprandial hyperglycemia.
- Pharmacological Classification: Antidiabetic combination comprising a biguanide (Metformin) and an alpha-glucosidase inhibitor (Voglibose).
- Mechanism of Action: Metformin decreases hepatic glucose production, increases insulin sensitivity, and improves peripheral glucose uptake. Voglibose inhibits alpha-glucosidase enzymes in the small intestine, delaying carbohydrate digestion and absorption, thus reducing postprandial glucose spikes.
Alternate Names
- This combination is often referred to as Vogmet.
- Several brand names exist depending upon the manufacturer; these can be confirmed at the dispensing pharmacy.
How It Works
- Pharmacodynamics: Metformin reduces hepatic glucose output, improves insulin sensitivity, and enhances peripheral glucose disposal. Voglibose delays the breakdown of complex carbohydrates into glucose in the intestine, blunting postprandial glucose increase.
- Pharmacokinetics:
- Metformin: Absorbed from the gastrointestinal tract, minimally protein-bound, not metabolized, and excreted renally.
- Voglibose: Minimally absorbed from the GI tract, exerts its action locally in the intestine, and what little is absorbed is excreted renally.
- Mode of Action:
- Metformin: Exact mechanism is unclear, but it activates AMP-activated protein kinase (AMPK), leading to the observed metabolic effects.
- Voglibose: Competitively and reversibly inhibits alpha-glucosidase enzymes located on the brush border of the small intestine.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation:
- Metformin: AMPK activation
- Voglibose: Alpha-glucosidase inhibition
- Elimination pathways:
- Metformin: Renal excretion
- Voglibose: Primarily fecal excretion; a small amount of absorbed drug is renally excreted.
Dosage
Standard Dosage
Adults:
- Initial: Voglibose 0.2 mg + Metformin 500 mg, one tablet three times daily with meals.
- Maintenance: Dosage titrated based on blood glucose levels, up to Voglibose 0.3mg + Metformin 1000mg, one tablet thrice daily with meals.
- Maximum daily doses: Voglibose 0.6 mg; Metformin 2550 mg (extended-release formulation), 3000 mg (immediate-release formulation).
- Geriatric patients (≥ 65 years): Initiate at lower doses due to age-related decline in kidney function. Adjust based on GFR and tolerability.
Children:
- Metformin monotherapy is approved for children ≥10 years old, and Voglibose in combination with Metformin is recommended in children above 10 years of age.
- Voglibose + Metformin combination dosage for children needs to be individualized, and caution is advised.
Special Cases:
- Elderly Patients: Start with lower doses and titrate cautiously, monitoring renal function.
- Patients with Renal Impairment: Contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²). Adjust dose based on eGFR for moderate impairment.
- Patients with Hepatic Dysfunction: Contraindicated in patients with hepatic insufficiency due to increased risk of lactic acidosis with metformin.
- Patients with Comorbid Conditions: Individualized dosing is required. Consult latest guidelines.
Clinical Use Cases
The listed use cases of intubation, surgical procedures, mechanical ventilation, ICU use and emergency situations are not applicable to this medication. Metformin + Voglibose is specifically indicated for the chronic management of type 2 diabetes mellitus. It is not relevant to acute or emergency situations typically encountered in those settings.
Dosage Adjustments
- Renal/hepatic dysfunction: Adjust dosage as mentioned above.
- Metabolic disorders: Individualized dosing may be necessary.
- Genetic polymorphisms affecting drug metabolism: Exercise caution.
Side Effects
Common Side Effects
- Gastrointestinal: Flatulence, diarrhea, abdominal pain, nausea, changes in taste.
Rare but Serious Side Effects
- Lactic Acidosis (Metformin): Rare but life-threatening.
- Hepatotoxicity: Monitor liver function tests.
- Hypoglycemia (especially when combined with sulfonylureas or insulin): Dizziness, sweating, confusion, palpitations.
Long-Term Effects
- Vitamin B12 deficiency (Metformin): Monitor B12 levels during long-term use.
Adverse Drug Reactions (ADR)
- Lactic acidosis, severe hypoglycemia, hepatotoxicity, angioedema.
Contraindications
- Hypersensitivity to metformin or voglibose.
- Severe renal impairment.
- Hepatic impairment.
- Diabetic ketoacidosis.
- Inflammatory bowel disease, colonic ulceration, intestinal obstruction.
- Conditions predisposing to increased intestinal gas formation.
- Congestive heart failure requiring pharmacological treatment.
- Acute/chronic metabolic acidosis.
Drug Interactions
- Antidiabetic drugs (e.g., sulfonylureas, insulin): Increased risk of hypoglycemia.
- Drugs affecting renal function: May affect metformin elimination.
- Alcohol: Increased risk of lactic acidosis and hypoglycemia.
- Miconazole: Increased risk of hypoglycemia with glimepiride (when included in triple therapy).
- Colesevelam: Reduced glimepiride absorption (when included in triple therapy).
Pregnancy and Breastfeeding
- Metformin: Pregnancy Category B. Transfer of Metformin through the placenta and into human milk is documented.
- Voglibose: Negligible systemic absorption suggests low risk to the fetus or neonate; however, data is limited.
- Consult specialized guidelines regarding the use of Metformin and Voglibose during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: See above.
- Side Effects: See above.
- Contraindications: See above.
- Drug Interactions: See above.
- Pregnancy & Breastfeeding: Consult specialized guidelines.
- Dosage: See above.
- Monitoring Parameters: HbA1c, fasting and postprandial blood glucose, renal function (eGFR, creatinine), liver function tests (especially at initiation and dose changes of Metformin), vitamin B12 (during long-term Metformin use).
Popular Combinations
- This combination itself is a popular one. Triple therapy may include a sulfonylurea (e.g., glimepiride) or a thiazolidinedione (e.g., pioglitazone) in addition to metformin and voglibose.
Precautions
- Monitor for hypoglycemia, gastrointestinal side effects, lactic acidosis (Metformin), and vitamin B12 deficiency (Metformin).
- Renal and hepatic function should be assessed before initiating therapy and periodically thereafter.
- Assess for contraindications.
FAQs (Frequently Asked Questions)
A: See the dosage section above. Dosing should be individualized based on patient characteristics, comorbidities and response to treatment.
Q2: What are the most common side effects?
A: Gastrointestinal side effects, such as flatulence, diarrhea, abdominal pain, and nausea, are common.
Q3: Can this combination be used in patients with renal impairment?
A: Contraindicated in severe renal impairment. Use with caution and dose adjustment in moderate renal impairment.
A: Lactic acidosis is a rare but serious metabolic complication characterized by the buildup of lactic acid in the blood. Metformin can increase the risk, especially in patients with renal impairment.
A: Consult specialized guidelines for the use of metformin and voglibose during pregnancy and lactation. Safety data, especially for voglibose, is limited.
Q6: How does this combination interact with alcohol?
A: Alcohol can increase the risk of both lactic acidosis (with metformin) and hypoglycemia. Advise patients to limit alcohol intake.
Q7: Are there any long-term effects of this combination?
A: Metformin can cause vitamin B12 deficiency with long-term use. Monitor B12 levels.
A: HbA1c, fasting and postprandial glucose, renal and hepatic function, and vitamin B12 levels during long-term use.
Q9: How does Voglibose interact with other antidiabetic medications?
A: When combined with other antidiabetic agents, particularly insulin or sulfonylureas, the risk of hypoglycemia is increased. Careful dose adjustments and blood glucose monitoring is required.
