Development of incretin-based treatments: From single GLP-1 therapy to combined dual and triple hormone therapies for metabolism

Up to 24% body weight reduction has been observed with dual and triple agonists in metabolic disease management.

• Incretin-based therapies, including GLP-1 receptor agonists and dual/triple agonists, are evolving in the treatment of type 2 diabetes, obesity, and liver diseases.
• DPP-4 inhibitors provide modest benefits, while GLP-1 receptor agonists like liraglutide and semaglutide show significant weight loss and cardiometabolic advantages.
• Tirzepatide (dual agonist) and retatrutide (triple agonist) demonstrate unprecedented efficacy, achieving up to 24% body weight reduction and improved liver and inflammatory markers.
• New agents like cotadutide and efinopegdutide extend treatment options to metabolic dysfunction-associated liver diseases.
• Challenges remain in cost, accessibility, and the lack of representation from low- and middle-income countries in major clinical trials.

Simplified