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Insulin Degludec/Ryzodeg

Insulin Degludec (marketed as Tresiba®) and its combination product Ryzodeg® (Insulin Degludec + Insulin Aspart) are advanced insulin therapies designed to manage diabetes mellitus. Insulin Degludec is an ultra-long-acting basal insulin, while Ryzodeg combines it with rapid-acting Insulin Aspart to provide both basal and prandial coverage. This article integrates evidence from the British National Formulary (BNF)Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to detail their mechanisms, clinical uses, dosing, side effects, precautions, drug interactions, and pharmaceutical nomenclature.

  1. Insulin Degludec:
    • Ultra-Long Duration: Forms multi-hexamers at the subcutaneous injection site, slowly releasing monomers into the bloodstream. This results in a flat, stable pharmacokinetic profile lasting over 42 hours, mimicking physiological basal insulin (Lippincott).
    • Glucose Regulation: Binds to insulin receptors, promoting cellular glucose uptake and suppressing hepatic glucose production (Lange).
  2. Ryzodeg (Insulin Degludec/Aspart):
    • Dual Action: Combines 70% ultra-long-acting Insulin Degludec with 30% rapid-acting Insulin Aspart.
      • Basal Coverage: From Degludec.
      • Prandial Coverage: From Aspart, which acts within 10–20 minutes to control post-meal glucose spikes (BNF).
  1. BNF-Approved Indications:
    • Insulin Degludec:
      • Type 1 Diabetes: Basal insulin in flexible dosing regimens.
      • Type 2 Diabetes: Monotherapy or combined with oral agents/GLP-1 agonists.
    • Ryzodeg:
      • Type 1 and Type 2 Diabetes: For patients requiring both basal and mealtime insulin (BNF).
  2. Special Populations:
    • Gestational Diabetes: Limited data; use under specialist supervision.
    • Elderly: Requires cautious titration due to hypoglycemia risk (Lange).
  • Insulin Degludec (Tresiba®):
    • Initial Dose:
      • Type 1 Diabetes: 0.2–0.4 units/kg/day.
      • Type 2 Diabetes: 10 units daily or 0.1–0.2 units/kg/day.
    • Titration: Adjust every 3–4 days based on fasting glucose.
    • Flexible Dosing: Can be administered at any time of day, with ≥8 hours between doses (BNF).
  • Ryzodeg:
    • Dosage: Administered once or twice daily with major meals.
    • Initial Dose: Individualized; typically 0.2–0.4 units/kg/day.
    • Max Dose: No strict maximum; guided by glycemic targets (BNF).
  • Renal/Hepatic Impairment:
    • Degludec: Dose reduction may be needed in severe impairment.
    • Ryzodeg: Monitor closely; avoid in severe hepatic failure (Lippincott).
  1. Common:
    • Hypoglycemia: Most frequent, especially with missed meals or overdosing.
    • Weight Gain: Moderate (2–5 kg) due to anabolic effects.
    • Injection Site Reactions: Lipodystrophy, itching, or rash (BNF).
  2. Rare but Serious:
    • Hypersensitivity: Angioedema, anaphylaxis.
    • Hypokalemia: Insulin shifts potassium intracellularly; monitor in at-risk patients (Lange).
  • Contraindications:
    • Hypersensitivity to insulin or excipients.
    • Ryzodeg: Avoid during episodes of hypoglycemia.
  • Special Populations:
    • Pregnancy: Use only if benefits outweigh risks (BNF advises insulin as preferred therapy).
    • Elderly: Start with lower doses to minimize hypoglycemia.
    • Regular blood glucose, HbA1c, and renal/hepatic function.
    • Assess injection sites for lipodystrophy (Lippincott).
  1. Hypoglycemia Risk Enhancers:
    • Sulfonylureas, GLP-1 Agonists: Synergistic glucose-lowering effects.
    • Beta-Blockers: Mask hypoglycemia symptoms (e.g., tremor, tachycardia).
  2. Hyperglycemia Inducers:
    • Corticosteroids, Thiazides: Counteract insulin’s effects.
  3. Other Interactions:
    • ACE Inhibitors, Lithium: May alter insulin sensitivity (BNF).
  • Insulin Degludec:
    • Generic: Insulin Degludec.
    • Brand Names: Tresiba® (UK/US), Xultophy® (combination with liraglutide).
  • Ryzodeg:
    • Generic: Insulin Degludec/Insulin Aspart.
    • Brand Name: Ryzodeg® (UK/US).

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