Usage
- Glipizide + Metformin is prescribed for type 2 diabetes mellitus in adults. It is used as an adjunct to diet and exercise to improve glycemic control when these measures alone are insufficient. It is sometimes prescribed after failure on other medications. This combination medicine is not indicated for type 1 diabetes.
- Pharmacological Classification: Antidiabetic combination containing a sulfonylurea (glipizide) and a biguanide (metformin).
- Mechanism of Action: Glipizide stimulates insulin release from pancreatic beta-cells. Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity.
Alternate Names
- Glipizide/Metformin Hydrochloride
- Brand Names: Metaglip (discontinued)
How It Works
- Pharmacodynamics: Glipizide increases insulin secretion, leading to lower blood glucose levels. Metformin improves insulin sensitivity, reduces hepatic glucose production and decreases gastrointestinal glucose absorption.
- Pharmacokinetics:
- Absorption: Both drugs are orally absorbed, with glipizide reaching peak plasma concentration in 1-3 hours (immediate release) and 6-12 hours (extended release). Metformin reaches peak plasma concentration in approximately 2.5 hours.
- Metabolism: Glipizide is primarily metabolized in the liver by CYP2C9. Metformin is not metabolized.
- Elimination: Glipizide metabolites are excreted renally. Metformin is excreted unchanged in the urine.
- Mode of Action: Glipizide binds to sulfonylurea receptors on pancreatic beta-cells, closing ATP-sensitive potassium channels, leading to depolarization and calcium influx, triggering insulin release. Metformin’s precise mechanism is not fully understood, but it is thought to activate AMP-activated protein kinase (AMPK), leading to the observed metabolic effects.
Dosage
Standard Dosage
Adults:
- Initial: 2.5 mg glipizide/250 mg metformin orally once daily with a meal. If fasting plasma glucose is 280-320 mg/dL, start with 2.5 mg/500 mg twice daily. For second-line therapy (after other medications): start at 2.5 mg/500 mg or 5 mg/500 mg twice daily.
- Maintenance: Increase in increments of 2.5 mg glipizide/250 mg (or 500 mg) metformin every 2 weeks as needed, based on blood glucose levels.
- Maximum: 20 mg glipizide / 2000 mg metformin daily in divided doses.
Children:
- Not recommended for pediatric patients.
Special Cases:
- Elderly Patients: Start with a low dose and titrate cautiously due to increased risk of hypoglycemia and renal impairment.
- Patients with Renal Impairment: Contraindicated in patients with an eGFR < 30 mL/min/1.73 m². Not recommended to initiate in patients with eGFR 30-45 mL/min/1.73 m². Dose adjustments may be necessary in patients with mild to moderate renal impairment.
- Patients with Hepatic Dysfunction: Avoid use in patients with hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with heart failure or other conditions that may predispose them to lactic acidosis.
Clinical Use Cases
Glipizide + Metformin is specifically indicated for chronic management of type 2 diabetes. It is not typically used in acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Insulin is generally preferred in these scenarios for tighter glycemic control.
Dosage Adjustments
Dose adjustments are required for renal impairment and should be based on eGFR. Start low and titrate slowly in older adults.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea
- Upset stomach
- Headache
- Upper respiratory tract infections
Rare but Serious Side Effects:
- Hypoglycemia
- Lactic acidosis
- Hepatotoxicity
- Hemolytic anemia (especially in patients with G6PD deficiency)
Long-Term Effects:
- Vitamin B12 deficiency
- Increased risk of cardiovascular events (although rare)
Adverse Drug Reactions (ADR):
- Severe hypoglycemia requiring medical intervention
- Lactic acidosis (muscle pain, trouble breathing, stomach pain, vomiting, irregular heart rate, dizziness, feeling cold, weakness)
- Allergic reactions (hives, difficulty breathing, angioedema)
Contraindications
- Hypersensitivity to glipizide or metformin
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
- Acute or chronic metabolic acidosis (including diabetic ketoacidosis)
- Type 1 diabetes
Drug Interactions
- CYP2C9 Inhibitors/Inducers: These can alter glipizide metabolism, necessitating dosage adjustments.
- Drugs that decrease renal function: Can increase the risk of lactic acidosis with metformin (e.g., iodinated contrast media).
- Alcohol: Increases the risk of hypoglycemia and lactic acidosis.
- Cimetidine: Can increase metformin levels.
Pregnancy and Breastfeeding
- Pregnancy: Insulin is generally recommended for managing diabetes during pregnancy. While glipizide and metformin cross the placenta, their effects on the fetus are not well-established.
- Breastfeeding: Both drugs are excreted in breast milk. A decision should be made to discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Glipizide: Stimulates insulin release; Metformin: Decreases hepatic glucose production, increases insulin sensitivity, and reduces intestinal glucose absorption.
- Side Effects: Diarrhea, nausea, headache, hypoglycemia, lactic acidosis (rare).
- Contraindications: Severe renal impairment, metabolic acidosis, hypersensitivity.
- Drug Interactions: CYP2C9 inhibitors/inducers, alcohol, cimetidine, iodinated contrast media.
- Pregnancy & Breastfeeding: Consult a specialist; potential fetal/neonatal risks exist.
- Dosage: Start low and titrate based on blood glucose levels. Maximum 20 mg/2000 mg daily.
- Monitoring Parameters: Blood glucose, HbA1c, renal function (eGFR), vitamin B12 levels.
Popular Combinations
Not applicable since this is already a combination product.
Precautions
- Renal function monitoring is essential.
- Risk of lactic acidosis, especially with renal impairment, dehydration, or iodinated contrast media use.
- Hypoglycemia risk is present, particularly with alcohol consumption or skipped meals.
FAQs (Frequently Asked Questions)
A: Initial: 2.5 mg/250 mg once daily with food. Titrate every 2 weeks as needed. Maximum: 20mg/2000 mg daily. Adjust dosage for renal impairment and in the elderly.
Q2: What are the major side effects?
A: The most common side effects are gastrointestinal (diarrhea, nausea, upset stomach).
Q3: What are the contraindications for this medication?
A: Contraindications include severe renal impairment, metabolic acidosis, and hypersensitivity.
Q4: Can this drug be used in pregnancy?
A: Insulin is generally preferred during pregnancy. Consult a specialist for advice.
Q5: How does this combination work?
A: Glipizide stimulates insulin release, while metformin improves insulin action and reduces hepatic glucose output.
Q6: What should patients be advised about lifestyle modifications?
A: Patients should be counseled on the importance of diet, exercise, and regular blood glucose monitoring.
A: Lactic acidosis is rare but serious. The risk increases with renal impairment, dehydration, and certain drug interactions.
Q8: How should hypoglycemia be managed?
A: Consume a fast-acting source of glucose (e.g., fruit juice, glucose tablets). Glucagon may be administered for severe hypoglycemia.
A: This medication can be used with other diabetes medications, but careful monitoring for drug interactions and adverse effects is crucial.
Q10: Are there any long-term side effects of this medication?
A: Vitamin B12 deficiency can occur with long-term metformin use. Regular monitoring is recommended.
