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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.
- 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).
- 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).
- Dual Action: Combines 70% ultra-long-acting Insulin Degludec with 30% rapid-acting Insulin Aspart.
- 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).
- Insulin Degludec:
- 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).
- Initial Dose:
- 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).
- 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).
- 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).
- Hypoglycemia Risk Enhancers:
- Sulfonylureas, GLP-1 Agonists: Synergistic glucose-lowering effects.
- Beta-Blockers: Mask hypoglycemia symptoms (e.g., tremor, tachycardia).
- Hyperglycemia Inducers:
- Corticosteroids, Thiazides: Counteract insulin’s effects.
- 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).
