Generic Name

Mechanism of Action

Mechanism

Insulin lispro is a rapid‑acting recombinant insulin analog.
• Rapid absorption: Contains a proline‑arginine substitution (position B28‑B29) preventing hexamer formation, allowing immediate monomeric uptake.
• Binding: Quickly engages the insulin receptor on hepatocytes, adipocytes, and myocytes, stimulating the PI3K/Akt pathway for glucose uptake and inhibiting hepatic gluconeogenesis.
• Action profile: Onset ~15 min, peak 30–90 min, duration 4–6 h, ideal for mealtime glucose blunting.

Pharmacokinetics

• Absorption: Subcutaneous injection → pharmacokinetic curve similar to human rapid‑acting analogs.
• Peak times: 30–90 min post‑injection.
• Duration: 4–6 h (may vary with injection site and volume).
• Metabolism: Primarily renal; no active metabolites.
• Half‑life: 1–1.5 h (systemic).
• Interaction: Minimal drug‑drug interactions; avoid concurrent use with other rapid‑acting insulins.

Indications

• Type 1 diabetes mellitus – for postprandial glucose control in combination with basal insulin.
• Type 2 diabetes mellitus – adjunct to basal insulin, oral agents, or GLP‑1 agonists.
• Correction of hyperglycemia – when rapid correction is needed.
• Gestational diabetes – safe in pregnancy when paired with appropriate basal coverage.

Contraindications

• Hypersensitivity to insulin, recombinant DNA products, or excipients (e.g., metacresol).
• Severe renal or hepatic impairment – dose adjustments may be necessary; monitor closely.
• Crisis management: Use with caution during ketoacidosis or hyperosmolar states; ensure adequate ketosis risk assessment.
• Pregnancy: Generally safe; FDA category B; use under specialist guidance.
• Lactation: Insulin passes into breast milk; relative risk is low but should be balanced against maternal glycemic benefit.

Dosing

• Pre‑meal dosing: 0.2–0.3 U/kg or 4–10 U per meal, depending on individual insulin sensitivity.
• Timing: 15–30 min before meals; not recommended 5 min after.
• Basal–bolus strategy: Combine with long‑acting insulin or other basal units.
• Pen vs vial: Prefer pens for accuracy and reducing contamination.
• Sites: Abdomen, thighs, upper arm; rotate sites to prevent lipodystrophy.
• Continuous subcutaneous infusion (CSII): 0.1–0.6 U/hr infusion rate; monitor for infusion site isolates.
• Dose adjustments: Titrate to fasting/planning glucose targets; use SMBG or CGM readings.

Adverse Effects

Common:
• Hypoglycemia (most frequent with meal‑time insulin).
• Lipohypertrophy or lipoatrophy at injection site.
• Injection‑site pruritus or erythema.
• Mild weight gain.

Serious:
• Severe hypoglycemia with loss of consciousness.
• Allergic reactions (urticaria, angioedema).
• Rare anaphylaxis.
• Cardiac ischemia (no evidence of direct effect but beware in patients with comorbid heart disease).

Monitoring

• Blood glucose: Pre‑meal, post‑meal (15–30 min), bedtime, and CGM trends.
• HbA1c: Every 3 months or more frequently per clinical status.
• Body weight & BMI: Monitor for chronic weight gain.
• Lipodystrophy: Inspect injection sites weekly.
• Renal function: Creatinine & eGFR at baseline and periodically.
• Ketones: In type 1 patients, especially if hypoglycemia episodes are frequent.
• Blood pressure & lipids: Routine monitoring.

Clinical Pearls

• PALM Principle: *Pre‑meal, 15‑30 min, Late/late sweetener* – yes, paracetamol, 15 min.
• Do not mix insulin lispro with regular insulin or R‑type analogs; can cause heterodimerization and altered PK.
• Pen storage: Keep at room temperature (15–25 °C). Avoid freeze/thaw; discard if ice forms.
• Hi‑frequency patients: Consider CSII for precision; basal‑bolus titration should prioritize post‑prandial glucose (<140 mg/dL) to minimize hypoglycemia risk.
• Pregnancy: Start at 6–8 weeks GA; adjust for insulin sensitivity changes during each trimester.
• Diabetic ketoacidosis (DKA): When using insulin lispro in DKA, serial blood glucose with balanced IV fluids; watch for rebound hypoglycemia as ketones resolve.
• Weight management: Pair with low‑glycemic‑index meals and regular exercise to counteract mild weight gain.

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• Key terms: insulin lispro, rapid‑acting insulin, postprandial control, basal‑bolus regimen, hypoglycemia, lipodystrophy.