Insulin glargine (Lantus) provides 24-hour basal insulin coverage. Which physicochemical property accounts for its prolonged, peakless action?

• A Attachment of a fatty acid chain to lysine-29 promotes reversible albumin binding in the bloodstream, extending half-life
• B Substitution of proline-28 prevents hexamer dissociation, delaying absorption from subcutaneous tissue
• C Polyethylene glycol conjugation prevents renal clearance, extending action to 24 hours
• D Substitution of asparagine-21 with glycine and addition of two arginines at C-terminus shifts the isoelectric point to pH 7.0, causing precipitation at physiological pH and slow dissolution from the subcutaneous depot ✓

Explanation

Glargine is engineered with glycine substitution at A21 and two arginine residues added at B30, shifting the isoelectric point to approximately 6.7–7.0 (nearly neutral pH). When injected subcutaneously at pH 7.4, the solution micro-precipitates into crystals that dissolve slowly, creating a protracted absorption profile lasting ~24 hours with no pronounced peak. Insulin detemir (not glargine) uses fatty acid (myristic acid) conjugation for albumin binding to extend action.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.