Semaglutide (weekly GLP-1 RA) produces greater weight loss than liraglutide (daily GLP-1 RA). The pharmacokinetic feature explaining semaglutide's extended half-life is:
- A Semaglutide is a shorter peptide that is filtered less by the glomerulus, reducing renal clearance
- B Semaglutide has a C18 fatty diacid attached via a hydrophilic linker, producing tighter albumin binding and substantially slower DPP-4 and NEP degradation compared with liraglutide's C16 fatty acid attachment ✓
- C Semaglutide contains multiple D-amino acid substitutions at positions 8 and 34 that prevent dipeptidyl peptidase-4 cleavage
- D Semaglutide is formulated in a depot microsphere matrix (PLGA) that provides sustained subcutaneous release over 7 days
Correct answer: B. Semaglutide has a C18 fatty diacid attached via a hydrophilic linker, producing tighter albumin binding and substantially slower DPP-4 and NEP degradation compared with liraglutide's C16 fatty acid attachment
Explanation
Semaglutide has two structural modifications: an Aib8 substitution (alpha-amino isobutyric acid at position 8, resisting DPP-4 cleavage) and a C18 fatty diacid moiety attached via a long hydrophilic spacer. The C18 diacid enables much stronger albumin binding than liraglutide's C16 fatty acid — increasing the half-life to ~168 hours (allowing once-weekly dosing) versus liraglutide's ~13 hours. The stronger albumin binding also substantially slows renal clearance and peptidase degradation.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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