The Metabolic Trio
Semaglutide, tirzepatide, retatrutide — three generations of the same story. As effects grow, so do the questions. Compare evidence, not ads.
Editorial introduction
This is the best-documented peptide class ever: semaglutide (STEP, SUSTAIN, SELECT — tens of thousands of participants), tirzepatide (SURPASS, SURMOUNT, and SURMOUNT-5 which put it in the ring with semaglutide) and retatrutide, whose phase II delivers the largest effect ever recorded — along with the most open questions.
How to read this series: notice the difference between 'approved drug with years of data' and 'phase II with 300 people'. For semaglutide and tirzepatide we know both how many kilograms leave and what happens when therapy stops. For retatrutide we know the effect impresses — and that is roughly it.
The shared question for all three: who loses muscle while the kilograms leave, and what does a therapy that does not stop mean. That is not a peptide problem — it is the whole class's problem.
Reading list
- 01Semaglutideanalog
GLP-1 analog with an extended half-life (~7 days), enabling weekly dosing; basis of Ozempic, Wegovy, Rybelsus.
Approved drugStrong evidence - 02Tirzepatideanalog
Dual GIP/GLP-1 receptor agonist with weekly half-life; drugs Mounjaro, Zepbound.
Approved drugStrong evidence - 03Retatrutideanalog
Triple GIP/GLP-1/glucagon receptor agonist, in development as a subcutaneous anti-obesity drug.
Clinical trialsModerate evidence - 04Cagrilintideanalog
A long-acting amylin analogue — reduces appetite via the area postrema.
Clinical trialsModerate evidence - 05Tesamorelinanalog
Analog of human GHRH(1–44) with an N-terminal trans-3-hexenoyl modification — FDA-approved drug (Egrifta SV).
Approved drugStrong evidence