A patient with Type 2 DM is switched from insulin glargine to insulin degludec. The physician explains that degludec forms multi-hexameric depot subcutaneously, leading to its ultra-long action. This depot dissolves at which rate, providing its PK advantage?
- A Rapid initial dissolution, then slow absorption — producing an early peak followed by a flat profile
- B pH-dependent precipitation at subcutaneous tissue pH of 7.4, dissolving at a fixed daily rate
- C Zero-order dissolution from the multi-hexameric depot, producing a peakless, stable absorption profile over 42+ hours ✓
- D Albumin-bound depot that releases slowly over 24 hours via saturable albumin binding sites
Explanation
Insulin degludec forms di-hexamers in the formulation (containing phenol and zinc). After subcutaneous injection, these assemble into long multi-hexameric chains. Albumin binds zinc from the outer hexamers, slowly dissolving the chain in a near zero-order fashion. This results in an ultra-long peakless action profile (duration >42 hours), allowing once-daily dosing with reduced nocturnal hypoglycaemia risk. Glargine's mechanism is different: it precipitates as microcrystals due to the acidic formulation reacting with neutral subcutaneous tissue pH, giving it a long but not as flat a profile. Degludec does bind albumin at the periphery but the multi-hexameric depot dissolution is the primary PK mechanism.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.