Insulin Lispro

Usage

• Insulin Lispro is prescribed for the treatment of Type 1 and Type 2 diabetes mellitus in adults and children (3 years and older). It is used to improve glycemic control by mimicking the body’s natural insulin response to meals.
• Pharmacological Classification: Rapid-acting human insulin analog.
• Mechanism of Action: Insulin Lispro initiates its action by binding to insulin receptors on cell membranes. This binding facilitates glucose uptake into cells, primarily in muscle and adipose tissue, and inhibits hepatic glucose production, ultimately lowering blood glucose levels.

Alternate Names

• International/Regional Variations: Insulin lispro
• Brand Names: Humalog, Admelog, Lyumjev

How It Works

• Pharmacodynamics: Insulin Lispro exerts its glucose-lowering effect by binding to insulin receptors on target cells. It promotes glucose uptake in muscle and fat cells and inhibits hepatic glucose output, thus regulating postprandial glucose levels.

• Pharmacokinetics:

  • Absorption: Subcutaneous absorption is rapid, with peak concentrations generally occurring within 30-90 minutes. Intravenous administration results in an immediate effect.
  • Metabolism: Primarily metabolized in the liver and kidneys, similar to human insulin.
  • Elimination: Excreted via urine and feces.

• Mode of Action: Binds to the insulin receptor tyrosine kinase, triggering intracellular signaling pathways that promote glucose transport, glycogen synthesis, and protein synthesis.

• Receptor Binding: Binds specifically to the insulin receptor.

• Elimination Pathways: Hepatic and renal metabolism and excretion.

Dosage

Standard Dosage

Adults (Type 1 Diabetes):

• 0.4-1.0 unit/kg/day subcutaneously, divided into multiple doses, typically given before meals (within 15 minutes before or immediately after). The total daily dose is often divided, with one-third administered as basal insulin and the remainder as bolus insulin before meals. Dose adjustments are made based on blood glucose levels and individual needs.
• Continuous subcutaneous infusion (insulin pump): The total daily dose from the previous multiple-dose injection regimen should be used to initiate pump therapy, dividing roughly 50% as basal and 50% as bolus.

Adults (Type 2 Diabetes):

• Starting dose: 4 units subcutaneously before the largest meal or the meal with the highest postprandial glucose. Alternatively, 10% of the total daily basal insulin dose can be given. If HbA1c is below 8%, consider decreasing the basal insulin dose by the same amount. Increase the dose by 1–2 units or 10%–15% twice weekly to improve glycemic control, as needed.
• Often used in combination with intermediate- or long-acting insulin.

Children (Type 1 Diabetes, ≥3 years):

• 0.4-1.0 unit/kg/day subcutaneously, divided into multiple doses before meals, similar to adult dosing. Dosage requirements might increase during puberty.

Special Cases:

• Elderly Patients: Dosage should be individualized, starting at a lower end of the range and titrated based on blood glucose control. Close monitoring for hypoglycemia is important.
• Patients with Renal Impairment: Dose reductions may be necessary as renal function declines.
• Patients with Hepatic Dysfunction: Dose adjustment might be required due to potential changes in insulin clearance.
• Patients with Comorbid Conditions: Consider comorbidities such as cardiovascular disease when adjusting insulin doses and optimizing glycemic targets.

Clinical Use Cases

• Intravenous Infusion (U-100 only): Administer diluted Insulin Lispro (0.1-1 unit/mL in normal saline) under strict medical supervision for managing hyperglycemia in hospital settings, especially in situations requiring rapid glucose control.
• Surgical Procedures: Insulin infusion may be used to maintain perioperative glycemic control.
• Intensive Care Unit (ICU) Use: Insulin infusions are common for managing hyperglycemia in critically ill patients.

Dosage Adjustments

• Adjustments are necessary based on patient-specific factors like blood glucose monitoring results, changes in diet or physical activity, renal or hepatic impairment, and intercurrent illnesses.

Side Effects

Common Side Effects

• Hypoglycemia (low blood sugar)
• Injection site reactions (pain, redness, swelling)
• Weight gain

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 at the injection site)

Contraindications

• Hypoglycemia
• Hypersensitivity to insulin lispro or any of its excipients

Drug Interactions

• Medications that can increase the risk of hypoglycemia: oral hypoglycemic agents, ACE inhibitors, salicylates, alcohol.
• Medications that can reduce the hypoglycemic effect of Insulin Lispro: corticosteroids, atypical antipsychotics, thiazide diuretics.
• Beta-blockers can mask symptoms of hypoglycemia.

Pregnancy and Breastfeeding

• Insulin Lispro is generally considered safe during pregnancy. Dosage adjustments are often needed throughout pregnancy.
• Insulin Lispro can be used during breastfeeding. Dose adjustments may be needed.

Drug Profile Summary

• Mechanism of Action: Binds to insulin receptors, facilitating glucose uptake and suppressing hepatic glucose production.
• Side Effects: Hypoglycemia, injection site reactions, weight gain.
• Contraindications: Hypoglycemia, hypersensitivity.
• Drug Interactions: Numerous drug interactions, impacting both efficacy and risk of hypoglycemia.
• Pregnancy & Breastfeeding: Generally considered safe with dosage adjustments.
• Dosage: Individualized based on diabetes type, age, and other factors.
• Monitoring Parameters: Blood glucose levels, HbA1c, potassium levels.

Popular Combinations

• Basal insulin (e.g., glargine, detemir)

Precautions

• General Precautions: Careful blood glucose monitoring, proper injection technique, awareness of hypoglycemia symptoms.
• Specific Populations: Dosage adjustments and close monitoring are essential for elderly patients, and those with renal or hepatic impairment. Pediatric dosing should be guided by weight and blood glucose levels.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Insulin Lispro?

A: Dosage is individualized based on patient factors. Typical starting doses are 0.4–1.0 units/kg/day for type 1 diabetes and 4 units before the largest meal for type 2 diabetes.

Q2: How quickly does Insulin Lispro work?

A: Onset of action is rapid, typically within 15 minutes, making it suitable for pre-meal injections. Peak action occurs within 30-90 minutes.

Q3: What are the signs and symptoms of hypoglycemia?

A: Sweating, tremors, anxiety, confusion, palpitations, hunger, dizziness, and blurred vision. Severe hypoglycemia can lead to seizures and loss of consciousness.

Q4: Can Insulin Lispro be used in pregnancy?

A: Yes, Insulin Lispro is generally considered safe to use during pregnancy but requires careful monitoring and dose adjustments.

Q5: What are the main drug interactions with Insulin Lispro?

A: Numerous drugs can interact with Insulin Lispro, including certain oral antidiabetics, beta-blockers, and corticosteroids. Consult a comprehensive drug interaction resource for details.

Q6: What are the storage recommendations for Insulin Lispro?

A: Unopened vials and pens should be refrigerated. Once in use, vials, pens, and cartridges can be kept at room temperature for up to 28 days, away from direct sunlight and excessive heat.

Q7: How should Insulin Lispro be administered?

A: Administered subcutaneously using a syringe, pen device, or insulin pump. For IV infusion, U-100 should be diluted in normal saline. U-200 formulations should not be used intravenously or in insulin pumps.

Q8: What is the difference between Insulin Lispro and regular human insulin?

A: Insulin Lispro is a rapid-acting insulin analog with a quicker onset and shorter duration of action compared to regular human insulin.

Q9. Can patients switch between different brands of insulin lispro?

A: While they are biosimilar, switching between brands should be done under medical supervision, as minor adjustments to the dosage might be necessary.