Insulin Lispro

Approved Indications:

• Type 1 Diabetes Mellitus: For glycemic control in adults and pediatric patients requiring insulin for daily management.
• Type 2 Diabetes Mellitus: As part of a basal-bolus regimen in adults when oral agents are insufficient.
• Diabetic Ketoacidosis (DKA): Used in hospital settings as part of an intravenous insulin protocol.

Clinically Accepted Off-Label Uses:

• Gestational Diabetes Mellitus (GDM): For pregnant patients when diet and exercise alone are insufficient.
• Hyperkalemia (Adjunctive): Used with glucose to shift potassium intracellularly in acute hyperkalemia.
• Continuous Subcutaneous Insulin Infusion (CSII): As part of insulin pump therapy for patients needing precise control.

• Route: Subcutaneous (SC) injection, continuous SC infusion (via insulin pump), or intravenous infusion (hospital setting).
• Adult & Pediatric Dosing: Individualized based on blood glucose monitoring and carbohydrate intake.
• Typical Starting Total Daily Dose (TDD): 0.4–1.0 units/kg/day divided between basal and bolus insulin.
• Pre-Meal Dosing: Administer within 15 minutes before or immediately after meals.
• CSII (Insulin Pump): Lispro is compatible for continuous subcutaneous infusion; basal rates adjusted individually.
• Intravenous Use: For DKA or severe hyperglycemia under hospital supervision.
• Special Populations:
• Renal Impairment: Increased risk of hypoglycemia; consider dose reduction.
• Hepatic Impairment: May require dose adjustment and close monitoring.
• Elderly: Start cautiously and monitor for hypoglycemia.
• Duration of Action: Rapid onset (within 15 min), peak at 30–90 min, duration 3–5 hours.

Insulin lispro is a rapid-acting human insulin analog designed by reversing the amino acids at positions 28 and 29 on the B-chain (proline and lysine). This structural change prevents hexamer formation, allowing faster dissociation into active monomers after injection. Insulin lispro binds to insulin receptors on target tissues (liver, muscle, fat), activating the receptor’s tyrosine kinase activity. This initiates a cascade that promotes glucose uptake via GLUT4 transporters, enhances glycogen synthesis, suppresses hepatic gluconeogenesis, and reduces lipolysis and proteolysis, ultimately lowering blood glucose levels.

• Absorption: Rapid absorption after SC injection; onset ~15 minutes.
• Bioavailability: ~55–77%.
• Distribution: Widely distributed in extracellular fluid; does not cross BBB significantly.
• Metabolism: Metabolized by insulin-degrading enzyme primarily in liver and kidneys.
• Half-Life: Approximately 1 hour (biological effect lasts 3–5 hours).
• Elimination: Excreted via renal metabolism and urinary clearance.
• Onset/Peak/Duration: Onset 10–15 min; peak 30–90 min; duration 3–5 hours.

• Pregnancy: Classified as Category B (no evidence of harm in animal studies; limited human data suggest safety). Commonly used in pregnancy for glycemic control.
• Lactation: Insulin is excreted in small amounts in breast milk but is not orally active in infants; considered safe during breastfeeding.
• Caution: Monitor maternal blood glucose closely; adjust dose as pregnancy progresses.

• Primary Class: Antidiabetic agent.
• Subclass: Rapid-acting insulin analog.

• Known hypersensitivity to insulin lispro or any excipient.
• During episodes of hypoglycemia.
• Use in insulin pump if device malfunction is suspected without backup insulin.

• Severe Hypoglycemia: Monitor closely; risk increases with missed meals or excessive dosing.
• Hypokalemia: Insulin drives potassium into cells; monitor in patients at risk.
• Driving/Machine Use: Risk of hypoglycemia may impair ability.
• Illness or Stress: May require dose adjustment.
• Pump Therapy Risks: Infusion set occlusion or device failure may lead to rapid onset of hyperglycemia or ketoacidosis.
• Switching Insulins: Requires medical supervision to prevent hypo- or hyperglycemia.

Common (≥10%):

• Endocrine: Hypoglycemia (most frequent adverse effect).
• Injection Site: Pain, redness, lipodystrophy.

Less Common (1–10%):

• Weight gain.
• Peripheral edema.

Rare but Serious:

• Severe allergic reactions (anaphylaxis).
• Localized or generalized insulin allergy.
• Hypokalemia leading to cardiac arrhythmias.

• Drug-Drug:
• Hypoglycemia Risk Increased by: Oral antidiabetic agents, beta-blockers, salicylates, alcohol.
• Hyperglycemia Risk Increased by: Corticosteroids, diuretics, sympathomimetics, thyroid hormones.
• Drug-Food: No significant interactions, but carbohydrate intake timing affects efficacy.
• Alcohol: Can enhance hypoglycemic effect.
• Enzyme Systems: Not significantly metabolized by CYP450; interactions mainly pharmacodynamic.

• ADA and WHO guidelines continue to recommend rapid-acting analogs like lispro as first-line bolus therapy for type 1 diabetes and in selected type 2 diabetes patients needing mealtime coverage.
• Recent updates emphasize time-in-range monitoring and individualized insulin-to-carb ratio for precision therapy.
• Continuous glucose monitoring (CGM) integration with insulin lispro use in pump therapy strongly recommended.

• Unopened Vials/Pens: Refrigerate at 2°C to 8°C; do not freeze.
• In-Use Pens/Vials: Can be kept at room temperature (below 30°C) for up to 28 days.
• Light Protection: Keep away from direct heat and sunlight.
• Handling: Do not use if solution is cloudy or contains particles.
• Pump Reservoirs: Replace every 7 days or as per manufacturer’s instructions.