Insulin

Mechanism of Action of Insulin

  • What is insulin? (Slide 2–3)

    • hormone produced by pancreatic beta cells.

    • Promotes glucose uptake for energy or storage as glycogen.

    • Regulates glucose homeostasis and prevents hyperglycemia/hypoglycemia.

  • Mechanism of action (Slides 4–6)

    • Insulin binds to insulin receptor (a tyrosine kinase receptor).

    • Stimulates GLUT-4 translocation → increased glucose entry into muscle and fat cells.

    • Promotes:

      • Glucose ➝ glycogen (liver, muscle).

      • Glucose ➝ fatty acids (adipose tissue).

      • Glucose ➝ pyruvate (glycolysis).

    • Key outcome: control of postprandial blood glucose.

2. Characteristics of Different Classes of Insulin

  • Types (Slide 7):

    • Rapid acting (lispro, aspart, glulisine). black

    • Short acting (regular). blue

    • Intermediate (NPH, mixes). pink

    • Long acting (detemir, glargine, degludec). green

    • Concentrated (U-500, U-200).

    • Inhaled (Afrezza).

    • the longer they last in body more risk for hyperglycemia

Rapid-acting Insulin (Slides 8–22)

  • Examples - Lispro (Humalog®, Admelog® biosimilar, Lyumjev®)

    • comes in U-100 and U-200 forms as pen and vials

    • Aspart (Novolog®, Fiasp®), Glulisine (Apidra®) all considered medically equivalent and interchangeable but still need new Rx to switch

  • Onset: ~15 min - 30 (Lyumjev/Fiasp slightly faster 12–13 min)

  • Peak: 1–3 hours. Duration: 3–5 hours.

  • Use: Bolus (mealtime); only class used in insulin pumps.

  • Special: U-200 lispro available 200 units/mL rest the same less volume less discomfort ; Fiasp contains nicotinamide (Vit B3 aka niacin) for faster absorption

Short-acting Insulin (Slides 23–25)

  • Regular insulin (Humulin R, Novolin R).

  • Onset: ~30 min. Peak: 2.5–5 h. Duration: 4–12 h.

  • Uses - IV infusion for diabetic emergencies DKA, HHS, TPN

    • less used outpatient due to slow onset and long duration vs. rapid-acting.

Intermediate-acting Insulin (Slides 26–30)

  • NPH (Neutral Protamine Hagedorn).

  • Cloudy suspension — must roll gently to mix (not shake).

  • Onset: 1–2 h. Peak: 4–12 h. Duration: 14–24 h.

  • Use - for cost-sensitive patients and in premixed products to cover liver glucose

Pre-mixed Insulin (Slides 31–34)

  • Combination of NPH + rapid/regular.

  • Examples: Humalog Mix 25/50, Novolog Mix 70/30, Novolin 70/30.

  • Onset: 15–30 min, Peak: 2–4 h, Duration: 14–24 h.

  • Reduces injections but less flexibility for individualized dosing.

Mixing Insulin (Slides 29–30)

  • Only mix rapid/short-acting + NPH. Do NOT mix with long-acting.

  • Steps:

    1. Add air to NPH vial.

    2. Add air to rapid/short-acting vial.

    3. Draw rapid/short-acting first.

    4. Then draw NPH.

  • Reason: Rapid/short-acting is clear; NPH is cloudy. NPH contamination would distort dosing.

Long-acting Insulin (Slides 35–46)

  • Detemir (Levemir®): 6–23 h, albumin binding, expected withdrawal 2026.

  • Glargine (Lantus®, Basaglar®, Semglee® U-100; Toujeo® U-300): 24 h or longer, peakless, forms micro precipitates that dissolve based on pH

  • Degludec (Tresiba®): >42 h duration, flat absorption, U-100/U-200, long stability (8 weeks after opening).

    • same pen but have different max, units/pen, dose settings, concentration

    • injected as long chains that dissociate from the ends

    • Typically once-daily, but some require BID.

Concentrated Insulin (Slides 47–49)

  • U-500 Regular: onset ~30 min, peak ~2–5 h, duration 12–24 h.

  • Used for insulin-resistant patients needing large doses.

  • onset like regular but duration of NPH

Inhaled Insulin (Afrezza®, Slides 50–53)

  • Onset: 12–15 min, Peak: ~1 h, Duration: 3 h.

  • Delivered via inhaler with cartridges (4, 8, 12 units).

  • Alternative to injections; not suitable in asthma or COPD.

  • units of 4 on the cartridges blue 4 green 8 yellow 12

3. Biosimilar Insulin (Slides 44–46)

  • Since March 2020, insulin regulated as biologic, allowing biosimilars.

    • Highly similar to approved biologic, with no meaningful clinical difference.

  • Can be interchanged at the pharmacy if designated as interchangeable.

  • Examples:

    • Semglee (glargine) biosimilar to Lantus.

    • Admelog (lispro) biosimilar to Humalog.

    • Basaglar (glargine) – similar but not technically a biosimilar at approval (now under biologic framework).

5. Choosing Appropriate Insulin for Therapy

  • Depends on patient characteristics, cost, timing of meals, lifestyle:

    • Rapid-acting ➝ mealtime coverage, flexible eating habits.

    • Regular ➝ inpatient use.

    • NPH ➝ cost-effective, 1–2 daily injections (but higher hypoglycemia risk).

    • Premix ➝ fewer injections but less flexibility.

    • Long-acting ➝ stable basal levels; fewer hypoglycemic events (esp. with degludec).

    • U-500 ➝ for insulin resistance with very high daily dose needs.

    • Afrezza ➝ needle-free bolus option (but restricted in lung disease).

6. Novel Insulins (Slides 47, 54)

  • Investigational pipeline (Slide 54):

    • Insulin icodec (weekly basal) — once-weekly dosing, improves adherence.

    • Insulin icosema (icodec + semaglutide dual agent).

    • Eli Lilly also testing weekly formulations.

  • Current innovations:

    • Longest-acting currently approved = degludec (>42h).

    • Weekly administration may significantly reduce injection burden, especially for type 2 diabetes.