Usage
This combination is primarily prescribed for Polycystic Ovary Syndrome (PCOS) in women of reproductive age to improve insulin sensitivity, regulate menstrual cycles, and manage metabolic aspects of the syndrome. Metformin is an antihyperglycemic agent (biguanide), and Myo-inositol is an insulin-sensitizing agent that acts as a second messenger in insulin signaling pathways.
Alternate Names
Metformin is also known as dimethylbiguanide. Myo-inositol may simply be referred to as inositol. There isn’t an official alternate name for this combination drug. Brand names vary, and ZEROMET-MYO is one example marketed in India.
How It Works
Metformin:
- Pharmacodynamics: Decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity in peripheral tissues.
- Pharmacokinetics: Absorbed from the gastrointestinal tract, not extensively metabolized, and excreted renally. Minimal hepatic metabolism.
- Mode of Action: Activates AMP-activated protein kinase (AMPK), a key cellular energy sensor, leading to reduced hepatic gluconeogenesis.
Myo-inositol:
- Pharmacodynamics: Improves insulin sensitivity and signaling by acting as a second messenger in the phosphatidylinositol 3-kinase (PI3K) pathway. May improve ovarian function in PCOS.
- Pharmacokinetics: Absorbed from the GI tract. Metabolized and excreted.
- Mode of Action: Improves glucose uptake and utilization in peripheral tissues by influencing insulin signaling pathways.
Elimination Pathways: Metformin is renally cleared. Myo-inositol metabolic pathways and excretion are less defined.
Dosage
Standard Dosage
Adults:
In PCOS, a common dosage is Metformin 500 mg + Myo-inositol 600 mg twice daily, taken with meals. Treatment may extend for 6 months or longer depending on individual patient responses.
Children:
The combination is typically not used in children. Metformin alone can be considered for adolescents with type 2 diabetes or PCOS.
Special Cases:
- Elderly Patients: Close monitoring of renal function is essential. Dosage adjustments may be needed based on eGFR.
- Patients with Renal Impairment: Metformin dosage needs to be adjusted or avoided altogether based on the stage of renal impairment (eGFR).
- Patients with Hepatic Dysfunction: Metformin should be used with caution in mild to moderate hepatic impairment and avoided in severe impairment due to the risk of lactic acidosis.
- Patients with Comorbid Conditions: Carefully assess the risks and benefits of metformin in individuals with heart failure, liver disease, or significant respiratory disease.
Clinical Use Cases
Metformin + Myo-inositol is not typically used in acute care settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. In such scenarios, metformin is usually held, especially when nil per os (NPO) is required.
Dosage Adjustments
Dose adjustments for metformin are crucial in renal or hepatic impairment. Consult specific guidelines for dose reductions based on eGFR levels. Myo-inositol dosage adjustments are less defined in such cases.
Side Effects
Common Side Effects
- Gastrointestinal issues (diarrhea, nausea, vomiting, abdominal discomfort) are the most frequent with metformin.
Rare but Serious Side Effects
- Lactic acidosis (a rare but serious metabolic complication, primarily with metformin).
Long-Term Effects
- Vitamin B12 deficiency (may occur with long-term metformin use).
Adverse Drug Reactions (ADR)
Contraindications
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²) for metformin.
- Acute or chronic metabolic acidosis.
- Hepatic failure.
- Hypersensitivity to metformin or myo-inositol.
Drug Interactions
- Alcohol (increases the risk of lactic acidosis with metformin).
- Iodinated contrast media (temporarily discontinue metformin).
- Cationic drugs (may compete with metformin for renal tubular secretion).
- Some diuretics (may affect renal function and metformin clearance).
Pregnancy and Breastfeeding
Metformin is generally considered safe during pregnancy (Category B). Myo-inositol also has a relatively safe profile in pregnancy. However, always weigh the benefits against potential risks. Consult specialists if necessary. Limited information is available on excretion into breast milk. Caution is advised.
Drug Profile Summary
- Mechanism of Action: Metformin: Reduces hepatic glucose production, increases peripheral insulin sensitivity. Myo-inositol: Enhances insulin signaling.
- Side Effects: Primarily gastrointestinal (metformin).
- Contraindications: Renal failure (metformin).
- Drug Interactions: Alcohol, iodinated contrast, some medications affecting renal function.
- Pregnancy & Breastfeeding: Relatively safe; individual assessment required.
- Dosage: Adult PCOS: Metformin 500 mg + Myo-inositol 600 mg twice daily.
- Monitoring Parameters: Blood glucose, renal function (eGFR), vitamin B12 levels.
Popular Combinations
Metformin + Myo-inositol is itself a popular combination in PCOS.
Precautions
- General Precautions: Renal function assessment (eGFR). Monitor for lactic acidosis.
- Specific Populations: Age-specific dose adjustments in elderly patients. Renal/hepatic impairment necessitates dosage modifications or avoidance of metformin.
- Lifestyle Considerations: Limit alcohol intake during metformin therapy.
FAQs (Frequently Asked Questions)
A: A typical dose is Metformin 500 mg + Myo-inositol 600 mg twice daily with meals.
A: Metformin improves insulin sensitivity and reduces hepatic glucose production, while myo-inositol enhances insulin signaling and may improve ovarian function.
Q3: What are the common side effects?
A: Gastrointestinal issues (diarrhea, nausea, vomiting) are most common, primarily due to metformin.
Q4: Are there any serious side effects?
A: Lactic acidosis, though rare, is a serious potential side effect of metformin.
Q5: Can this combination be used during pregnancy?
A: Metformin and myo-inositol are generally considered safe in pregnancy but require a risk-benefit assessment.
Q6: What are the contraindications to using this combination?
A: Severe renal impairment, hepatic failure, and hypersensitivity are contraindications, particularly for metformin.
A: Yes, Metformin should be withheld pre- and post-operatively due to the risk of dehydration and lactic acidosis.
Q8: Are there any dietary restrictions with this combination?
A: No specific dietary restrictions apply to the combination itself, but taking metformin with meals is recommended to minimize gastrointestinal side effects.
A: Metformin dosage must be adjusted downward or avoided in patients with renal impairment based on their eGFR. Specific guidelines provide detailed recommendations.
A: Monitor renal function (eGFR), vitamin B12 levels, and blood glucose levels regularly.
