====== Insulin Degludec ======

Insulin degludec is an ultra-long-acting basal insulin analog used for background glucose control.

It provides a very flat, prolonged insulin profile lasting over 24 hours.

→ [[endocrine:insulin:start|Insulin Therapy]]

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===== Mechanism of Action =====

Degludec binds to the insulin receptor (tyrosine kinase receptor).

This activates:

  * IRS signaling pathways
  * PI3K/Akt cascade
  * GLUT4 translocation in muscle and adipose tissue

Physiologic effects:

Liver:
  * ↓ Hepatic gluconeogenesis
  * ↑ Glycogen synthesis

Muscle:
  * ↑ Glucose uptake

Adipose:
  * ↓ Lipolysis

As a basal insulin, its primary role is suppression of hepatic glucose production.

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===== Structural Modification & Protraction =====

Degludec differs from human insulin by:

  * Deletion of threonine at B30
  * Addition of a fatty acid side chain to B29 lysine

After subcutaneous injection:

  * Forms multi-hexamer chains
  * Creates a subcutaneous depot
  * Slowly releases insulin monomers over time

This produces:

  * Extremely flat pharmacokinetic profile
  * Very prolonged duration

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===== Pharmacokinetics =====

Onset:
  * ~1 hour

Peak:
  * Minimal peak (very flat profile)

Duration:
  * >42 hours

Half-life:
  * ~25 hours

Compared to:

  * [[endocrine:insulin:glargine|Glargine]]
  * [[endocrine:insulin:detemir|Detemir]]

Degludec has:

  * Longer duration
  * More stable day-to-day levels
  * Lower nocturnal hypoglycemia risk

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===== Clinical Use =====

  * Basal insulin in Type 1 Diabetes
  * Basal insulin in Type 2 Diabetes
  * Once-daily dosing

Often combined with:

  * Rapid-acting insulin (basal-bolus regimen)
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]
  * [[endocrine:biguanides:metformin|Metformin]]

Flexible dosing time (within reason) due to long half-life.

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===== Advantages =====

  * Ultra-long duration
  * Very flat profile
  * Lower nocturnal hypoglycemia risk
  * Reduced glucose variability

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===== Adverse Effects =====

  * Hypoglycemia
  * Weight gain
  * Injection site reactions

Lower hypoglycemia risk compared to some older basal insulins.

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===== Degludec vs Other Basal Insulins =====

[[endocrine:insulin:glargine|Glargine]]:
  * Long-acting
  * Once daily
  * Slight peak possible

[[endocrine:insulin:detemir|Detemir]]:
  * May require twice daily dosing
  * Shorter duration

Degludec:
  * Longest duration
  * Most stable pharmacokinetics
  * Flexible dosing window

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===== Clinical Pearls =====

  * Ultra-long-acting basal insulin
  * Suppresses hepatic glucose output
  * Minimal peak
  * Lower nocturnal hypoglycemia
  * Once-daily flexible dosing
  * Ideal for basal-bolus regimens

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===== Related =====

  * [[endocrine:insulin:start|Insulin Therapy]]
  * [[endocrine:insulin:glargine|Glargine]]
  * [[endocrine:insulin:detemir|Detemir]]
  * [[endocrine:diabetes:start|Diabetes Pharmacology]]