Dulaglutide is a GLP-1 receptor agonist with a half-life allowing once-weekly dosing. The prolonged action is achieved by:
- A Fusion to an IgG4-Fc domain creating a large protein resistant to DPP-4 degradation and renal filtration ✓
- B Acylation with a fatty acid chain enabling albumin binding and slow release
- C Substitution of alanine at position 2 preventing DPP-4 cleavage combined with daily subcutaneous depot
- D Encapsulation in microspheres that dissolve over seven days
Correct answer: A. Fusion to an IgG4-Fc domain creating a large protein resistant to DPP-4 degradation and renal filtration
Explanation
Dulaglutide consists of two GLP-1 analogue chains fused to a modified IgG4 Fc domain. The large molecular size prevents renal filtration and the Fc domain extends half-life via FcRn-mediated recycling, while the structural modifications prevent DPP-4 degradation. Semaglutide uses fatty-acid acylation (albumin binding) for prolongation; exenatide (twice-daily) has simple DPP-4 resistant substitutions.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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