1. Clinical Overview
Insulin Lispro (25%) + Insulin Lispro Protamine (75%) is a biphasic premixed insulin analogue formulation. It consists of 25% rapid-acting insulin lispro and 75% intermediate-acting insulin lispro protamine suspension. This combination provides both a rapid onset to control postprandial glucose excursions and a prolonged duration to provide basal insulin coverage. It is a mainstay therapy for patients with type 1 and type 2 diabetes mellitus requiring a simplified insulin regimen, reducing the number of daily injections.
| Onset | Duration | Bioavailability |
|---|---|---|
| Within 15-30 minutes | Up to 24 hours | 55-77% (Subcutaneous) |
2. Mechanism of Action
Insulin lispro is an insulin analogue where the natural amino acid sequence at positions B28 (proline) and B29 (lysine) is reversed. This modification reduces the propensity for self-association into hexamers, allowing for faster absorption from subcutaneous tissue. The protamine-bound lispro component forms a crystalline suspension that delays absorption, providing an intermediate duration of action. The combination mimics both prandial and basal insulin secretion.
3. Indications & Uses
- Type 1 Diabetes Mellitus (as part of a regimen)
- Type 2 Diabetes Mellitus (when oral agents with or without basal insulin are insufficient)
4. Dosage & Administration
Adult Dosage: Highly individualized. Typically started at 0.2-0.4 units/kg/day or 10 units/day, divided into 2-3 injections (usually before breakfast and dinner). Dose is titrated based on pre-meal and bedtime blood glucose monitoring.
Administration: For subcutaneous use only. Inject into abdominal wall, thigh, buttocks, or upper arm. Rotate sites within a region. Administer immediately (within 15 minutes) before a meal. Before use, gently roll the vial/pen between palms 10 times until the suspension appears uniformly cloudy/ milky. Do not shake vigorously. Do not use if clumping, frosting, or precipitation is seen.
5. Side Effects
Common side effects may include:
- Hypoglycemia (most common)
- Injection site reactions (pain, itching, redness, swelling)
- Lipodystrophy (lipohypertrophy or lipoatrophy at injection sites)
- Weight gain
- Peripheral edema (especially upon initiation)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Oral Hypoglycemic Agents (Sulfonylureas, Meglitinides) | Additive glucose-lowering effect, increased hypoglycemia risk | Major |
| Corticosteroids (e.g., Prednisone) | Antagonize insulin effect, increase insulin requirements | Major |
| Beta-blockers (non-selective like Propranolol) | Mask tachycardia warning signs of hypoglycemia, may potentiate or impair recovery from hypoglycemia | Major |
| Thiazide Diuretics | May cause hyperglycemia, increasing insulin requirements | Moderate |
| ACE Inhibitors (e.g., Ramipril) | May enhance hypoglycemic effect | Moderate |
| Alcohol | Potentiates hypoglycemic effect and impairs gluconeogenesis; risk of delayed hypoglycemia | Major |
| Octreotide, Lanreotide | Alters glucose metabolism, may increase or decrease insulin need | Moderate |
| MAO Inhibitors, Anabolic Steroids | Potentiate hypoglycemic effect | Moderate |
7. Patient Counselling
- DO check blood sugar levels regularly as advised.
- DO inject immediately (within 15 min) before a major meal.
- DO rotate injection sites within an area to prevent lipodystrophy.
- DO gently roll the pen/vial to mix before each injection.
- DO carry a fast-acting sugar source (glucose tablets) at all times.
- DON'T shake the insulin vial/pen vigorously.
- DON'T inject into muscles, scars, or areas of lipodystrophy.
- DON'T skip or delay meals after injection.
- DON'T share pens or needles with anyone.
8. Toxicology & Storage
Overdose: Profound hypoglycemia: sweating, palpitations, tremor, anxiety, hunger, confusion, drowsiness, speech difficulty, headache, seizures, coma, and death if untreated.
Storage: Unopened (Refrigerated): Store at 2°C to 8°C. Do not freeze. Keep away from freezer compartment and direct sunlight. In-use (Opened): Vial/Pen in use can be kept at room temperature (below 30°C) for up to 28 days. Do not refrigerate the pen in use. Protect from excessive heat and light. Do not use if frozen, discolored, or contains particles. Keep out of reach of children.