Insulin glargin
1. Drug Name
Generic Name: Insulin Glargine
Brand Names: Lantus, Basaglar, Toujeo (varies by region)
2. Drug Classification
Class: Antidiabetic Agent
Subclass: Long-acting insulin analog
3. Mechanism of Action
Insulin glargine is a long-acting insulin analog that functions by mimicking the natural action of human insulin in regulating glucose metabolism. It binds to insulin receptors on various target tissues, including muscle and adipose tissue, facilitating the uptake of glucose into cells. This lowers blood glucose levels by promoting glucose storage and inhibiting hepatic glucose production.
Insulin glargine differs from human insulin in its amino acid sequence, which gives it a more prolonged duration of action. When injected subcutaneously, insulin glargine forms microprecipitates that slowly release insulin into the bloodstream, providing a steady, basal level of insulin with no pronounced peaks in action. This mimics the body’s natural insulin secretion, offering 24-hour control of blood glucose.
4. Pharmacokinetics
Absorption: Insulin glargine is absorbed slowly from the injection site, with peak concentrations occurring 4-6 hours after injection, but its onset of action is much slower compared to regular insulin. The duration of action is prolonged, providing a steady basal insulin level.
Distribution: Insulin glargine is widely distributed in the bloodstream, and like other insulin preparations, it binds to insulin receptors on muscle and fat tissues. Its volume of distribution (Vd) is approximately 0.05 L/kg.
Metabolism: Insulin glargine is metabolized in the liver and kidneys to form two active metabolites, M1 and M2. These metabolites retain insulin-like activity but do not exhibit the same duration of action as the parent compound.
Excretion: Insulin glargine and its metabolites are primarily excreted by the kidneys, with the half-life of the drug being approximately 12-19 hours.
Special Considerations:
Renal Impairment: Insulin glargine metabolism may be affected in patients with renal impairment, possibly leading to prolonged action and increased risk of hypoglycemia.
Hepatic Impairment: Hepatic impairment may also affect insulin glargine metabolism, necessitating dose adjustments.
5. Indications
Primary Indications:
Type 1 Diabetes Mellitus: Insulin glargine is used as a basal insulin in the treatment of type 1 diabetes, where it provides long-acting insulin coverage to control blood glucose levels throughout the day and night.
Type 2 Diabetes Mellitus: In patients with type 2 diabetes, insulin glargine is used to improve glycemic control when other oral medications or short-acting insulin therapies are insufficient.
Off-label Uses: Insulin glargine may be used off-label in the treatment of gestational diabetes or for patients with rare insulin resistance syndromes, though insulin is typically preferred in these cases.
Specific Populations: Insulin glargine is most beneficial for type 1 and type 2 diabetes patients who require a long-acting insulin to maintain basal insulin levels throughout the day and night.
6. Dosage and Administration
Adult Dosing:
For Type 1 Diabetes: Insulin glargine is typically initiated at a dose of 0.4–0.5 units/kg body weight per day, administered once daily. The dose is adjusted according to blood glucose levels.
For Type 2 Diabetes: The initial dose is usually 0.2 units/kg or 10 units once daily. Adjustments are made based on blood glucose monitoring.
Administration: Insulin glargine is administered subcutaneously once daily, preferably at the same time each day. The injection is typically given in the evening or at bedtime.
Renal Impairment Dosing: No specific dosage adjustments are recommended, but careful monitoring is advised due to the potential for prolonged insulin action and increased risk of hypoglycemia in patients with renal dysfunction.
Hepatic Impairment Dosing: Dosing may need to be adjusted in patients with liver disease, depending on the patient's individual needs and response to therapy.
Maximum Safe Dose: The maximum dose is individualized based on the patient's blood glucose levels, with adjustments made as needed to maintain control.
7. Contraindications
Absolute Contraindications:
Hypersensitivity to insulin glargine or any of its components.
Severe hypoglycemia or insulin overdose.
Relative Contraindications:
Caution in patients with renal or hepatic impairment due to the altered pharmacokinetics in these populations.
Use with caution in patients with a history of hypoglycemic unawareness.
8. Warnings and Precautions
Hypoglycemia: The most significant risk with insulin glargine is hypoglycemia, especially if the dose exceeds the body’s requirements or if patients skip meals. Signs of hypoglycemia include shakiness, sweating, confusion, and dizziness.
Hypokalemia: Insulin glargine can lead to a shift of potassium into cells, potentially causing hypokalemia. Electrolyte monitoring is recommended.
Allergic Reactions: Although rare, insulin glargine can cause allergic reactions, including local injection site reactions (e.g., redness, swelling, or itching), or more severe systemic allergic responses.
Insulin Overdose: An overdose of insulin glargine can result in severe hypoglycemia. Emergency measures, including glucose administration, should be taken.
Use with Other Medications: Careful monitoring is needed if insulin glargine is used with other medications that affect blood glucose levels, including oral hypoglycemic agents and corticosteroids.
9. Adverse Effects
Common Adverse Effects:
Hypoglycemia (most common).
Injection site reactions (e.g., redness, itching, or swelling).
Less Common but Clinically Significant Side Effects:
Lipodystrophy (localized fat tissue changes at injection sites).
Weight gain.
Rare/Serious Adverse Reactions:
Severe allergic reactions, including anaphylaxis.
Fluid retention and heart failure (more common with high-dose insulin therapy).
Severe hypokalemia, especially in high doses or with concomitant medications like diuretics.
10. Drug Interactions
Major Drug Interactions:
Oral Antidiabetic Agents: When used in combination with other hypoglycemic agents like metformin, sulfonylureas, or GLP-1 agonists, there is an increased risk of hypoglycemia. Dosage adjustments of insulin may be needed.
Corticosteroids: Corticosteroids can increase blood glucose levels, potentially requiring increased insulin doses.
Beta-blockers: Beta-blockers can mask the symptoms of hypoglycemia, such as tachycardia and tremors, making blood glucose monitoring essential.
Food-Drug Interactions: Insulin glargine can be administered without regard to meals, but patients should maintain consistent meal timing to avoid hypoglycemia.
Lab Test Interactions: Insulin therapy can affect the accuracy of some laboratory tests, especially those involving glucose measurements. Regular blood glucose monitoring is essential for dose adjustments.
11. Clinical Pharmacology
Pharmacodynamics: Insulin glargine provides a prolonged, steady release of insulin over 24 hours with minimal fluctuations, thus closely mimicking natural basal insulin secretion. This provides a stable insulin profile for maintaining blood glucose levels throughout the day.
Additional Pharmacological Effects: Insulin glargine may also have secondary benefits such as reducing protein catabolism and promoting anabolism, which helps in maintaining normal growth and tissue repair processes.
12. Special Populations
Pregnancy: Insulin glargine is classified as a pregnancy category C drug. Insulin is the preferred treatment for gestational diabetes, and insulin glargine may be used if blood glucose control cannot be achieved with other agents.
Lactation: Insulin glargine is excreted in human breast milk in small amounts. No significant adverse effects are expected on a breastfeeding infant, but insulin therapy should be monitored.
Geriatrics: Elderly patients may be at higher risk for hypoglycemia and require careful dose adjustments, especially if they have reduced renal or hepatic function.
Renal and Hepatic Dysfunction: Caution is needed in patients with kidney or liver disease. The pharmacokinetics of insulin glargine may be altered, necessitating closer monitoring of blood glucose and dose adjustments.
13. Therapeutic Uses
Type 1 Diabetes Mellitus: Used as a basal insulin in combination with short-acting insulins to control blood glucose throughout the day and night.
Type 2 Diabetes Mellitus: Used in patients with inadequate blood glucose control with oral agents to provide basal insulin coverage.
Gestational Diabetes: Can be used in pregnancy to control blood glucose levels in women who are insulin-dependent.
14. Monitoring and Follow-Up
Lab Tests: Regular monitoring of blood glucose levels (fasting and postprandial) and HbA1c levels. Renal function should be monitored in patients with impaired renal function.
Patient-Reported Symptoms: Patients should be educated to recognize signs of hypoglycemia, including shaking, sweating, dizziness, and confusion.
Monitoring Therapeutic and Toxic Levels: Blood glucose should be regularly monitored to maintain appropriate glycemic control and to prevent hypoglycemia.
15. Overdose Management
Symptoms of Overdose: Severe hypoglycemia, with symptoms including confusion, dizziness, sweating, and even coma.
Treatment Protocols: Administer glucose orally or intravenously if hypoglycemia occurs. In severe cases, glucagon injections may be needed.
Supportive Measures: Monitoring of blood glucose and electrolytes, and close observation in a healthcare setting may be required.
16. Patient Counseling Information
Key Points:
Take insulin glargine as prescribed, at the same time each day.
Avoid missing doses to ensure stable blood glucose levels.
Recognize the symptoms of hypoglycemia and carry glucose tablets or candy if you experience them.
Do not share insulin pens with others to avoid transmission of infections.
Consult your doctor if you experience unusual weight gain, swelling, or difficulty breathing.