What is the difference between retatrutide, tirzepatide and semaglutide?
Updated: 2026-09-09 · GLP-1 and weight
Short answer
They differ in how many pathways they activate and in their status. Semaglutide acts on one pathway, GLP-1. Tirzepatide acts on two, GLP-1 and GIP. Retatrutide is a triple agonist adding glucagon: it is not approved yet, although its manufacturer has reported positive phase 3 results and says it plans an FDA submission in the first quarter of 2027. More pathways does not automatically mean better for a given person.
In plain English
- Semaglutide: GLP-1 agonist, approved for specific indications.
- Tirzepatide: dual GLP-1/GIP agonist, approved for specific indications.
- Retatrutide: triple agonist, not approved yet, with phase 3 results reported by the manufacturer.
What we know
- In SURMOUNT-5, a phase 3b head-to-head trial published in 2025, tirzepatide produced a greater mean weight reduction than semaglutide at 72 weeks in adults with obesity and without diabetes. That result applies to that population and that trial.
- Gastrointestinal side effects are common across the class.
What we don't know yet
- How they compare over the very long term and what happens to weight after stopping each one.
Sources
External links to official sources or peer-reviewed studies.