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Pharmacology · Insulins

Insulin degludec !

An ultra-long-acting basal insulin. It forms chains of hexamers under the skin and lasts beyond a day, with a flat profile.

Updated 2026-11-01

  • Class: Insulins
  • Receptor: Insulin receptor
  • ATC code: A10AE06
  • WHO Model List of Essential Medicines

The figure shows human insulin bound to site 1 of an insulin receptor fragment. Degludec, once released as a monomer, binds the same receptor.

Target in 3D: Insulin receptor. PDB structure 4OGA (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Degludec lacks threonine B30 and carries a fatty diacid (hexadecanedioic acid) attached to lysine B29 through a glutamic acid spacer. After injection it assembles into long multi-hexamer chains that release monomers very slowly; the fatty chain also binds albumin. The free monomers activate the insulin receptor like human insulin.

  1. Fatty diacid chain makes degludec form multi-hexamers under the skin
  2. Monomers break off very slowly, also binding albumin
  3. Activates the insulin receptor like human insulin
  4. Flat basal effect that lasts beyond a day

Pharmacokinetics

Absorption
Subcutaneous; very slow release from the depot.
Half-life
About 25 hours at steady state, set mainly by absorption from the depot.
Onset and duration
Steady state is reached after 3 to 4 days of daily injections, so dose changes take days to show their full effect.

Indications

Adverse effects

Common

  • Hypoglycemia
  • Weight gain
  • Injection-site reactions, lipodystrophy and localized cutaneous amyloidosis
  • Low potassium

Contraindications

  • During an episode of hypoglycemia
  • Hypersensitivity to insulin degludec or an excipient

Key interactions

Beta-blockers, clonidine
Can blunt the warning signs of hypoglycemia.
Other glucose-lowering drugs
Raise the risk of hypoglycemia.
Corticosteroids, diuretics, atypical antipsychotics
Reduce the glucose-lowering effect.
Thiazolidinediones (pioglitazone)
Fluid retention and possible heart failure.

What is monitored

  • Fasting blood glucose, assessed over several days after a dose change
  • HbA1c
  • Injection sites

Administration and safety

  • Subcutaneous only: not given intravenously or in an insulin pump.
  • Never diluted or mixed with any other insulin or solution.
  • Pens come in more than one concentration: the pen delivers the dose shown, so syringes are never used to draw from a pen.
  • Pens, needles and syringes are never shared between patients.

Nursing care

  • Before: fasting glucose and the time of the last dose.
  • After a dose change, judge the effect over several days, not the next morning.
  • Watch for prolonged hypoglycemia; it may recur after treatment.
  • Teach the signs of hypoglycemia and site rotation.

Pregnancy and breastfeeding

Data in pregnancy are more limited than for human insulin or other analogues; when used, glucose is checked often.

Test yourself

Think of the answer, then tap the question to see it.

How does degludec achieve its very long action?

Its fatty diacid side chain makes it form multi-hexamer chains under the skin that release monomers very slowly; albumin binding adds to this.

Why are degludec dose changes judged over several days?

Steady state takes about 3 to 4 days, so the full effect of a change is not seen the next day.

Can degludec be used in an insulin pump or intravenously?

No. It is for subcutaneous injection only; pumps and IV infusions use rapid or regular insulin.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Insulin Degludec (rDNA Origin) Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - INSULIN DEGLUDEC injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 51 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.