Insulin Glargine

Usage

• Insulin glargine is a long-acting, human insulin analog prescribed for type 1 and type 2 diabetes mellitus to improve glycemic control. It is used to control high blood sugar in adults and children with type 1 diabetes and adults with type 2 diabetes.
• Pharmacological Classification: Antidiabetic Agent, Long-acting Insulin Analog.
• Mechanism of Action: Insulin glargine is engineered to have a low solubility at physiological pH. After subcutaneous injection, it forms microprecipitates in the subcutaneous tissue, resulting in a slow, prolonged release of insulin into the bloodstream over approximately 24 hours, providing a basal insulin level without pronounced peaks. This mimics the normal physiological secretion of basal insulin by the pancreas.

Alternate Names

• Insulin glargine, rDNA origin
• Brand Names: Lantus, Toujeo, Basaglar, Semglee, Rezvoglar

How It Works

• Pharmacodynamics: Insulin glargine exerts its effect by binding to insulin receptors on the surface of cells. This binding facilitates glucose uptake into muscle and fat cells, inhibits hepatic glucose production (gluconeogenesis), and promotes glycogen synthesis. It also inhibits lipolysis and proteolysis. The overall effect is a reduction in blood glucose levels.
• Pharmacokinetics:
  • Absorption: After subcutaneous injection, absorption is slow and prolonged, reaching a relatively constant concentration with no pronounced peak, which results in a duration of action of about 24 hours.
  • Metabolism: Insulin glargine is metabolized at the injection site, primarily by enzymatic degradation, with a minor contribution from hepatic metabolism.
  • Elimination: The elimination half-life is variable but averages around 24 hours. Elimination is primarily through metabolism at the injection site with no specific organs or pathways predominantly involved.
• Mode of Action: Glargine binds to the insulin receptor, a tyrosine kinase receptor. Receptor activation triggers a cascade of intracellular signaling events, including phosphorylation of insulin receptor substrates (IRS). This leads to increased glucose transporter (GLUT4) translocation to the cell membrane, facilitating glucose entry into cells.
• Receptor Binding: Binds to the insulin receptor.
• Enzyme Inhibition/Neurotransmitter Modulation: While insulin glargine primarily acts through receptor binding, it indirectly influences various enzymes involved in glucose metabolism, such as glycogen synthase and glycogen phosphorylase. It does not directly modulate neurotransmitters.
• Elimination Pathways: Primarily metabolized at the injection site with some contribution from the liver.

Dosage

Standard Dosage

Adults:

• The initial dose is individualized based on metabolic needs and blood glucose monitoring results.
• For insulin-naïve type 2 diabetes patients, a starting dose of 0.2 units/kg once daily is recommended, with subsequent adjustments as needed.
• For patients transitioning from other basal insulins, the dose should be adjusted based on the previous regimen.

Children (≥6 years for Type 1, ≥2 years for Type 2 - depending on the brand):

• Similar to adults, dosing is individualized based on metabolic needs, blood glucose monitoring, and treatment goals. Pediatric dosing requires careful titration. For type 1 diabetes, the initial dose is about one-third of the child’s total daily insulin requirements.
• Children younger than 2-6 (depending on the brand): Safety and efficacy have not been established.

Special Cases:

• Elderly Patients: Start with a lower dose due to potential age-related decline in renal function and increased sensitivity to insulin.
• Patients with Renal Impairment: Dose reduction may be required.
• Patients with Hepatic Dysfunction: Dose reduction may be required.
• Patients with Comorbid Conditions: Individualized dosing based on the specific comorbid condition and its impact on glucose metabolism.

Clinical Use Cases

• Insulin glargine is not indicated for the treatment of diabetic ketoacidosis (DKA). It is primarily used for long-term glycemic control in both inpatient and outpatient settings. Dosage adjustments may be necessary based on patient response and clinical situation.

Dosage Adjustments

• Dose adjustments are made based on self-monitored blood glucose (SMBG) readings and HbA1c levels. Titration should occur no more frequently than every 3-4 days for Toujeo (U-300) and can be more frequent with Lantus (U-100), with appropriate SMBG monitoring. Adjustments should always be done under medical supervision.

Side Effects

Common Side Effects:

• Hypoglycemia (low blood sugar)
• Injection site reactions (redness, swelling, pain, itching)
• Weight gain
• Edema (swelling)
• Upper respiratory tract infections

Rare but Serious Side Effects:

• Severe hypoglycemia (loss of consciousness, seizures)
• Severe allergic reactions (anaphylaxis)
• Hypokalemia (low potassium)

Long-Term Effects:

• Lipodystrophy (changes in subcutaneous fat tissue at the injection site)
• Weight gain

Adverse Drug Reactions (ADR):

• Anaphylaxis
• Severe hypoglycemia

Contraindications

• Hypersensitivity to insulin glargine or any of its components
• Episodes of hypoglycemia

Drug Interactions

• Many medications can interact with insulin glargine, including:
  • Other antidiabetic agents (e.g., sulfonylureas, meglitinides, thiazolidinediones): Increased risk of hypoglycemia.
  • Corticosteroids (e.g., prednisone): Decreased insulin effectiveness, leading to hyperglycemia.
  • Beta-blockers: May mask symptoms of hypoglycemia.
  • Alcohol: May increase the risk of hypoglycemia.
  • CYP450 inducers/inhibitors: Some drugs that affect CYP450 enzymes may alter insulin glargine metabolism.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: While there is no official FDA pregnancy category, data suggest insulin glargine is generally safe during pregnancy when clinically needed. However, careful glucose monitoring is crucial throughout pregnancy, as insulin requirements may fluctuate.
• Fetal Risks: Poorly controlled diabetes poses significant risks to both mother and fetus.
• Breastfeeding: Insulin glargine passes into breast milk but is not expected to harm nursing infants. Monitoring and dose adjustments may be needed during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Binds to insulin receptors, promoting glucose uptake and inhibiting hepatic glucose production.
• Side Effects: Hypoglycemia, injection site reactions, weight gain, edema.
• Contraindications: Hypersensitivity, hypoglycemia episodes.
• Drug Interactions: Numerous drug interactions, consult a comprehensive resource.
• Pregnancy & Breastfeeding: Generally considered safe with careful monitoring.
• Dosage: Individualized based on blood glucose levels; starting doses are typically 0.2 units/kg/day for adults.
• Monitoring Parameters: Blood glucose levels, HbA1c, potassium levels.

Popular Combinations

• Insulin glargine is often used in combination with bolus insulin (e.g., insulin lispro, aspart, glulisine) for optimal glycemic control in both type 1 and type 2 diabetes. This combined approach provides both basal and prandial insulin coverage.

Precautions

• General Precautions: Monitor blood glucose levels regularly, adjust dose as needed, rotate injection sites to prevent lipodystrophy.
• Specific Populations:
  • Pregnant Women: Careful glucose monitoring and dose adjustments throughout pregnancy.
  • Breastfeeding Mothers: Monitor infant and adjust dose as needed.
  • Children & Elderly: Start with lower doses and titrate carefully.
  • Lifestyle Considerations: Proper diet, regular exercise, and avoidance of alcohol are essential.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Insulin Glargine?

A: The initial dose is individualized based on patient needs and blood glucose levels. A common starting dose for insulin-naïve adults with type 2 diabetes is 0.2 units/kg/day, while adjustments are necessary for patients transitioning from other basal insulins. Pediatric dosing requires careful titration, with an initial dose of about one-third of the total daily insulin requirement for children with type 1 diabetes.

Q2: How is Insulin Glargine administered?

A: Insulin glargine is administered subcutaneously, typically once daily at the same time each day, preferably at bedtime. It should not be administered intravenously or intramuscularly.

Q3: Can Insulin Glargine be mixed with other insulins?

A: No, insulin glargine should not be mixed with any other insulin or solution. It should be injected separately.

Q4: What are the common side effects of Insulin Glargine?

A: Common side effects include hypoglycemia, injection site reactions (redness, swelling, pain), weight gain, and edema.

Q5: What should be done in case of suspected hypoglycemia?

A: Treat mild hypoglycemia with oral carbohydrates (e.g., glucose tablets, juice). Severe hypoglycemia may require glucagon injection or intravenous glucose administration. Seek medical attention if necessary.

Q6: Can Insulin Glargine be used during pregnancy?

A: While there are no controlled trials, data suggest it is generally safe to use insulin glargine during pregnancy when clinically needed. Careful glucose monitoring and dose adjustment are crucial during pregnancy, as insulin requirements may fluctuate.

Q7: Is Insulin Glargine safe during breastfeeding?

A: Yes, insulin glargine passes into breast milk, but it’s not expected to harm nursing infants. However, monitoring and dose adjustments may be needed during breastfeeding.

Q8: How should Insulin Glargine be stored?

A: Unopened vials and pens should be refrigerated. Once in use, they can be stored at room temperature for up to 28 days (check individual brand instructions). Avoid exposure to extreme temperatures and direct sunlight.

Q9: What are the signs and symptoms of severe hypoglycemia?

A: Severe hypoglycemia can manifest as loss of consciousness, seizures, confusion, and inability to respond. It requires immediate medical intervention.

Q10: Are there any specific dietary or lifestyle recommendations for patients on Insulin Glargine?

A: Patients on insulin glargine should follow a healthy diet, engage in regular physical activity, and avoid excessive alcohol consumption. Consistent carbohydrate intake is especially important to help manage blood glucose levels effectively. Close consultation with a dietitian or diabetes educator is advised.