Usage
Metformin + Repaglinide is prescribed for type 2 diabetes mellitus in adults. It is used as an adjunct to diet and exercise to improve glycemic control when metformin or repaglinide alone do not provide adequate control. It is not indicated for type 1 diabetes or diabetic ketoacidosis.
Its pharmacological classifications are:
- Metformin: Biguanide
- Repaglinide: Meglitinide
Mechanism of Action: Metformin decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity. Repaglinide stimulates insulin release from the pancreas.
Alternate Names
PrandiMet (brand name, discontinued). No other alternate names or international variations were found in the provided sources.
How It Works
Pharmacodynamics: Metformin primarily works by reducing hepatic glucose production and improving insulin sensitivity in peripheral tissues. Repaglinide works by binding to and closing ATP-dependent potassium channels in pancreatic beta-cells, leading to depolarization, calcium influx, and insulin secretion.
Pharmacokinetics:
- Metformin: Absorbed from the gastrointestinal tract, not metabolized, and excreted renally.
- Repaglinide: Rapidly absorbed, extensively metabolized by CYP450 enzymes (primarily CYP2C8 and CYP3A4), and excreted primarily in bile and feces.
Mode of Action: Metformin’s exact mechanism is not fully understood. It activates AMP-activated protein kinase (AMPK), leading to downstream effects on glucose metabolism. Repaglinide binds to specific sites on the pancreatic beta-cell sulfonylurea receptor, distinct from the sulfonylurea binding site. This leads to increased insulin secretion.
Elimination Pathways:
- Metformin: Renal excretion.
- Repaglinide: Hepatic metabolism, biliary and fecal excretion.
Dosage
Standard Dosage
Adults:
Initial dose: Varies depending on previous treatment.
- For patients inadequately controlled on metformin monotherapy: Repaglinide 1 mg + Metformin 500 mg twice daily with meals.
- For patients inadequately controlled on repaglinide monotherapy: Metformin 500 mg twice daily + existing repaglinide dose.
- For patients not previously on either medication: Repaglinide 0.5 mg (if HbA1c <8%) or 1-2 mg (if HbA1c ≥8%) + Metformin 500 mg with each meal.
The dose may be adjusted at 1–2 week intervals up to a maximum of 4 mg repaglinide with each meal. Maximum daily dose: Repaglinide 16 mg; Metformin 2500 mg.
Children:
Safety and efficacy not established in pediatric patients.
Special Cases:
- Elderly Patients: Initiate with a low dose and titrate cautiously, considering age-related decline in renal function.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73 m²). Use with caution in moderate renal impairment, adjusting the dose based on eGFR.
- Patients with Hepatic Dysfunction: Use with caution and adjust dose based on liver function.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustments may be required based on co-existing medical conditions, especially cardiovascular disease.
Clinical Use Cases
The provided sources do not specify dosage recommendations for specific medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments may be required based on renal or hepatic function, other medical conditions, concomitant medications, and individual patient response to therapy.
Side Effects
Common Side Effects
Hypoglycemia, headache, nausea, vomiting, diarrhea, upper respiratory tract infection.
Rare but Serious Side Effects
Lactic acidosis (especially in patients with renal impairment), severe hypoglycemia.
Long-Term Effects
Vitamin B12 deficiency.
Adverse Drug Reactions (ADR)
Severe hypoglycemia, lactic acidosis, allergic reactions (rash, itching, hives, swelling).
Contraindications
Hypersensitivity to repaglinide or metformin, type 1 diabetes, diabetic ketoacidosis, severe renal impairment (eGFR <30 mL/min/1.73 m²), acute or chronic metabolic acidosis, concomitant use of gemfibrozil.
Drug Interactions
Numerous drug interactions exist. Some notable ones include:
- CYP450 interactions: Repaglinide is metabolized by CYP2C8 and CYP3A4, and its levels can be affected by inhibitors or inducers of these enzymes.
- Drugs that may increase risk of hypoglycemia: Insulin, sulfonylureas, other antidiabetic medications.
- Drugs that may increase risk of lactic acidosis: Gemfibrozil, NPH insulin.
- Alcohol: Increases risk of hypoglycemia and lactic acidosis.
Pregnancy and Breastfeeding
- Pregnancy: Pregnancy Category C. Use only if clearly needed. Abnormal blood glucose levels during pregnancy are associated with congenital abnormalities.
- Breastfeeding: Not recommended. Both metformin and repaglinide are excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Metformin decreases hepatic glucose production and improves insulin sensitivity; repaglinide stimulates insulin release.
- Side Effects: Hypoglycemia, headache, gastrointestinal disturbances, lactic acidosis (rare).
- Contraindications: Type 1 diabetes, diabetic ketoacidosis, severe renal impairment, gemfibrozil use.
- Drug Interactions: Numerous drug interactions exist, especially with CYP450 modulators.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Individualized based on patient characteristics and prior therapy.
- Monitoring Parameters: Blood glucose (fasting and postprandial), HbA1c, renal function, vitamin B12 levels.
Popular Combinations
Often used in combination when metformin or repaglinide monotherapy fails to achieve adequate glycemic control. No other popular combinations were mentioned in the provided sources.
Precautions
Monitor renal function, vitamin B12 levels, and blood glucose regularly. Patients should be educated about the risk of hypoglycemia and lactic acidosis.
FAQs (Frequently Asked Questions)
A: The dosage is individualized. Refer to the Dosage section for detailed guidelines based on prior therapy, renal function, and other factors.
A: Take orally with meals, two to three times per day, within 15 minutes before eating. Skip the dose if a meal is skipped.
Q3: What are the common side effects of this medication?
A: Common side effects include hypoglycemia, headache, nausea, vomiting, and diarrhea.
Q4: What are the serious side effects I should be aware of?
A: Lactic acidosis and severe hypoglycemia are rare but serious side effects. Seek immediate medical attention if symptoms occur.
Q5: Can this medication be used during pregnancy or breastfeeding?
A: Generally, it is not recommended during pregnancy or while breastfeeding. Discuss with a physician to weigh the risks and benefits.
A: Contraindications include severe renal impairment, type 1 diabetes, diabetic ketoacidosis, and concomitant use of gemfibrozil.
Q7: Does this medication interact with other drugs?
A: Yes, it interacts with numerous medications. Inform your doctor about all other medications, including over-the-counter drugs and supplements.
Q8: What should I do if I miss a dose?
A: If a dose is missed, take it as soon as remembered unless it is close to the time for the next dose. Do not double the dose. If a meal is skipped, skip that dose of medication.
A: Metformin is not metabolized and is excreted renally. Repaglinide is extensively metabolized by the liver (CYP2C8 and CYP3A4) and excreted primarily in bile and feces.
