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.

→ Insulin Therapy

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.

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

Onset:

• ~1 hour

Peak:

• Minimal peak (very flat profile)

Duration:

• >42 hours

Half-life:

• ~25 hours

Compared to:

• Glargine
• Detemir

Degludec has:

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

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

Often combined with:

• Rapid-acting insulin (basal-bolus regimen)
• GLP-1 Receptor Agonists
• SGLT2 Inhibitors
• Metformin

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

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

• Hypoglycemia
• Weight gain
• Injection site reactions

Lower hypoglycemia risk compared to some older basal insulins.

Glargine:

• Long-acting
• Once daily
• Slight peak possible

Detemir:

• May require twice daily dosing
• Shorter duration

Degludec:

• Longest duration
• Most stable pharmacokinetics
• Flexible dosing window

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

• Insulin Therapy
• Glargine
• Detemir
• Diabetes Pharmacology