Dual Agonist
A single molecule that activates two different receptor types simultaneously to produce complementary therapeutic effects. Tirzepatide, which targets both GLP-1 and GIP receptors, is the most prominent dual agonist in the peptide therapeutics space and represents a major trend in metabolic drug development.
Technical Context
Tirzepatide is a single peptide that activates GLP-1R with approximately 5-fold lower potency than native GLP-1 and GIPR with approximately equal potency to native GIP. The SURPASS clinical trial programme demonstrated superior HbA1c reduction and the SURMOUNT programme demonstrated superior weight loss compared to selective GLP-1 RAs. The dual mechanism produces complementary effects — GLP-1R activation provides glucose-dependent insulin secretion, appetite suppression, and delayed gastric emptying, while GIPR activation may contribute additional metabolic and central appetite effects. The success of dual agonism has catalysed development of triple agonists (GLP-1R/GIPR/glucagon receptor) as next-generation metabolic therapies.