Tirzepatide, approved for type 2 diabetes and obesity, is a 'twincretin' because it acts as a dual agonist at which two receptors?

• A GLP-1 receptor and glucagon receptor
• B GLP-1 receptor and GIP (glucose-dependent insulinotropic polypeptide) receptor ✓
• C GLP-2 receptor and GIP receptor
• D GLP-1 receptor and Y2 neuropeptide receptor

Explanation

Tirzepatide is a synthetic peptide (based on GIP sequence) that acts as a dual agonist at both GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptors. GIP was previously thought to be a target of limited utility in T2DM because its insulinotropic effect is blunted; however, combined GIP+GLP-1 receptor activation demonstrates synergistic insulin secretion, greater HbA1c reduction, and superior weight loss compared to GLP-1 receptor agonists alone. Semaglutide acts only on GLP-1R. The GLP-1/glucagon dual agonist category (e.g., cotadutide) is a separate class. GLP-2R agonism promotes gut growth and has no glycaemic role.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.