Tirzepatide, approved for type 2 diabetes and obesity, differs from semaglutide in that it is a:

• A Triple GIP/GLP-1/glucagon receptor agonist providing additional glucagon-mediated fat oxidation
• B Dual GIP/GLP-1 receptor agonist (twincretin), exploiting synergistic insulinotropic and weight-reducing effects of both incretin pathways ✓
• C GLP-1 receptor agonist with additional direct DPP-4 inhibitory activity preventing GLP-1 degradation
• D GLP-1 receptor agonist combined with an SGLT2 inhibitor in a fixed-dose oral formulation

Explanation

Tirzepatide is a synthetic dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and GLP-1 receptor. It is a single peptide molecule that activates both incretin receptors simultaneously. The GIP component potentiates insulin secretion (especially at elevated glucose), reduces glucagon, and may contribute to adipose tissue lipid metabolism, while GLP-1 agonism suppresses appetite and slows gastric emptying. The SURPASS and SURMOUNT trials showed tirzepatide achieved greater weight loss (up to 22.5% in SURMOUNT-1) and HbA1c reduction than GLP-1 agonists alone. Retatrutide is the triple agonist under investigation.

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

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Written and medically reviewed by the StethoPrep medical team.