Degludec (insulin degludec) has a much longer half-life and lower day-to-day variability compared to glargine. The pharmacokinetic basis for this is:
- A It forms multi-hexameric chains and fatty acid binding to albumin creates a subcutaneous depot with slow dissociation of monomers ✓
- B It precipitates at subcutaneous pH 7.4 as a stable crystal, releasing slowly
- C It is absorbed directly into the lymphatic circulation bypassing capillary degradation
- D It is renally filtered and undergoes tubular reabsorption maintaining plasma levels
Correct answer: A. It forms multi-hexameric chains and fatty acid binding to albumin creates a subcutaneous depot with slow dissociation of monomers
Explanation
Insulin degludec has a C18 fatty di-acid attached via a glutamic acid linker to LysB29. At subcutaneous pH, degludec forms massive multi-hexameric chains held together by zinc and phenolic ligands. These large aggregates dissolve slowly, releasing monomers that subsequently bind albumin via the fatty acid chain — creating a systemic buffer depot. This dual-depot mechanism (subcutaneous + albumin-bound) produces an ultra-flat PK profile with >42-hour duration and coefficient of variability <20%, substantially less than glargine (~4% CV).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.