1. Clinical Overview
Insulin Lispro (50%) + Insulin Lispro Protamine (50%) is a biphasic premixed insulin analogue formulation. It consists of 50% rapid-acting insulin lispro and 50% intermediate-acting insulin lispro protamine suspension. This combination provides both a rapid onset of action to control postprandial glucose excursions and a prolonged duration to provide basal insulin coverage. It is a mainstay therapy for the management of type 1 and type 2 diabetes mellitus in the Indian population, offering convenience by reducing the number of daily injections.
| Onset | Duration | Bioavailability |
|---|---|---|
| 15-30 minutes | Up to 24 hours | 55-77% (Subcutaneous) |
2. Mechanism of Action
Insulin lispro is an insulin analogue where the natural proline at position B28 and lysine at B29 are reversed. This modification reduces the propensity for self-association into hexamers, allowing for more rapid absorption from subcutaneous tissue compared to regular human insulin. The insulin lispro protamine component is a suspension of insulin lispro crystals with protamine, which delays absorption, providing an intermediate duration of action. The combined formulation mimics both prandial and basal insulin secretion.
3. Indications & Uses
- Type 1 Diabetes Mellitus (insulin-dependent)
- Type 2 Diabetes Mellitus (in patients inadequately controlled on oral antidiabetic drugs (OADs) or where OADs are contraindicated)
4. Dosage & Administration
Adult Dosage: Highly individualized. Typically administered twice daily (before breakfast and before dinner). The total daily insulin requirement (TDD) in insulin-naïve type 2 patients is often started at 0.2-0.4 units/kg/day, with the 50/50 mix divided into two doses. Doses are adjusted based on self-monitored blood glucose (SMBG), primarily fasting and pre-meal values.
Administration: For subcutaneous use only. Inject into abdominal wall, thigh, buttocks, or upper arm. Rotate injection sites within the same region. Administer within 15 minutes before a meal. Before use, gently roll the vial/pen between palms 10 times and invert 10 times until it appears uniformly cloudy. Do not use if clear particles remain or if clumping occurs. Do not mix with any other insulin or diluent.
5. Side Effects
Common side effects may include:
- Hypoglycemia (most common)
- Injection site reactions (pain, redness, itching, swelling)
- Lipodystrophy (lipohypertrophy or lipoatrophy at injection site)
- Weight gain
- Peripheral edema (especially upon initiation)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Corticosteroids (e.g., Prednisolone) | Antagonize insulin effect, increasing blood glucose and insulin requirements. | Major |
| Beta-blockers (e.g., Propranolol) | May mask tachycardia during hypoglycemia and impair counter-regulatory response. Can also potentiate hypoglycemic effect. | Major |
| Thiazide Diuretics (e.g., Hydrochlorothiazide) | May cause hyperglycemia, increasing insulin requirements. | Moderate |
| ACE Inhibitors (e.g., Ramipril) | May enhance hypoglycemic effect. | Moderate |
| Sulfonylureas (e.g., Glimepiride) | Additive hypoglycemic effect, high risk of hypoglycemia. | Major |
| Alcohol | Potentiates hypoglycemic effect and impairs gluconeogenesis. Risk of delayed hypoglycemia. | Major |
| MAO Inhibitors, Anabolic Steroids | Potentiate hypoglycemic effect. | Moderate |
| Oral Contraceptives, Thyroid hormones, Sympathomimetics | May increase blood glucose, requiring dose adjustment. | Moderate |
7. Patient Counselling
- DO check blood sugar regularly as advised.
- DO inject within 15 minutes BEFORE a meal.
- DO rotate injection sites within the same body area.
- DO inspect the insulin; it should be uniformly cloudy. Do not use if clear.
- DO carry a sugar source (glucose tablets) at all times.
- DON'T skip meals after injection.
- DON'T share pens or needles.
- DON'T shake the vial/pen vigorously; roll gently.
- DON'T use if expired or improperly stored.
- DON'T drive or operate machinery if feeling hypoglycemic.
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 between 2°C to 8°C in refrigerator. Do not freeze. Keep away from cooling element. In-use (Room Temperature): Once in use, vials/pens can be kept at room temperature (below 30°C) for up to 28 days. Protect from direct heat and sunlight. Do not refrigerate the pen in use. Discard after 28 days, even if some insulin remains. Never use insulin that has been frozen or looks clumped, grainy, or has changed color.