Generic Name

t½

Mechanism

Insulin degludec is a recombinant human insulin analog where:
• A chain modification: Lys^18→Aib, Lys^16→Glu, plus a hexapeptide (R-D-P-A-P-A)—reversible covalent attachment to albumin.
• Albumin binding: Creates a subcutaneous depot that slowly releases monomers.
• Constant insulin: Provides a stable, basal suppression of hepatic glucose output with minimal peaks, reducing hypoglycaemia risk.

The drug’s action follows first‑order kinetics once released, mimicking physiological basal insulin.

Pharmacokinetics

• Absorption: Rapid, with peak at ~1–3 h post‑injection, but effect remains for >24 h.
• Half‑life: ~50 h, far exceeding other basal insulins.
• Distribution: Mainly extracellular fluid; albumin binding accounts for ~70 % of circulating drug.
• Metabolism: Cleaved by proteases to active insulin and excreted unchanged.
• Elimination: No renal or hepatic dependence; safe in mild–moderate kidney or liver impairment.

Indications

• Type 1 diabetes mellitus (T1DM)
• Type 2 diabetes mellitus (T2DM) (alone or add‑on to basal‑bolus therapy)
• Gestational diabetes when other basal therapies unsuitable
• Exchangeable with other basal insulins for patients requiring flexible timing

Contraindications

• Hypersensitivity to insulin or L‑actyl‑protein
• Cystic fibrosis or severe lipodystrophy (altered absorption)
• Severe renal or hepatic dysfunction is not contraindicated but monitor glucose
• Pregnancy: Category B; use when benefits outweigh risks
• Risk of hypoglycaemia: Due to prolonged action; careful titration in elderly, renal impairment, or hepatic disease

Warnings
• Long‑acting: May mask late hypoglycaemia; patient education essential.
• Lag time: Atypical hypoglycaemia risk if insulin and carbohydrate absorption happen concurrently.
• Multiple injections in <24 h: Unnecessary; may increase lipohypertrophy.

Dosing

1. Starting dose:
• T1DM: 0.3 U/kg/day (split into two injections)
• T2DM: 0.2–0.5 U/kg/day (adjust to HbA1c/fasting glucose targets)

2. Titration: Increase by 2 U every 3–4 days; aim for fasting glucose 4.4–5.6 mmol/L (80–100 mg/dL).

3. Injection sites: Subcutaneous (abdomen, thigh, or upper arm). Rotate sites to prevent lipodystrophy.

4. Timing flexibility: Dose can be given up to 8 h later than the previous dose with no efficacy loss.

5. Missed dose: Administer as soon as remembered; single‑dose escalation is not required.

Adverse Effects

• Common
• Hypoglycaemia (most frequent, especially nocturnal)
• Injection‑site reactions: erythema, induration
• Weight gain (average 0.5–1 kg/year)
• Serious
• Severe hypoglycaemia (requiring assistance)
• Allergic reactions (rare: rash, angioedema)
• Rare injection‑site nodules or abscess

Monitoring

| Lipid profile | Annually | 4 h after dose; adjust timing or dose accordingly.

Clinical Pearls

1. “Flex‑Dose” advantage – Dose can be shifted 8 h later without loss of control; ideal for shift workers or irregular schedules.
2. Rapid titration & reduced peak‑to‑trough variability – 18‑22 % lower glucose variability than glargine U300, translating to fewer hypoglycaemic events.
3. Albumin‑binding strategy – Allows once‑daily dosing in many patients; key for depot stability and ultra‑long action.
4. Switching from other basal insulins – Initiate at same U/kg dose; monitor for hypoglycaemia for first 2–3 weeks.
5. Use during pregnancy – Though not listed in G‑zonal guidelines, small registry data show similar safety profile to glargine; consider if dose optimisation unsatisfactory.
6. No partial‑pen penetration – Depicts minimal risk of accidental over‑dose; useful in low‑dose titrations.
7. Insulin‑derived peptide immunogenicity – Lower (>1 %) compared to other analogues; yet regular monitoring is advised in patients receiving large cumulative doses.

Takeaway: Insulin degludec offers a predictable, stable basal insulin platform with unmatched dosing flexibility, making it a cornerstone for optimized glycaemic management in both type 1 and type 2 diabetes.