If you have read anything about metabolic peptides, three names keep coming up: semaglutide, tirzepatide and retatrutide. They are not the same. Here is what the published research shows about how they differ.

Semaglutide: single-receptor GLP-1

Semaglutide is a GLP-1 receptor agonist. In the STEP 1 trial (Wilding et al., NEJM 2021), it produced a mean weight reduction of around 15% over 68 weeks in the studied population. It is the most extensively documented of the three.

Tirzepatide: dual GIP and GLP-1

Tirzepatide activates two receptors, GIP and GLP-1. In the SURMOUNT-1 trial (Jastreboff et al., NEJM 2022), the highest dose was associated with a mean reduction of roughly 20.9% over 72 weeks. The dual mechanism is the leading hypothesis for the larger average effect versus single-receptor agonists.

Retatrutide: triple agonist

Retatrutide targets three receptors, GIP, GLP-1 and glucagon. In a phase 2 trial (Jastreboff et al., NEJM 2023), the highest dose was associated with a mean reduction of about 24.2% at 48 weeks. As a newer compound, its long-term data set is still developing compared with the other two.

How researchers read the comparison

The pattern across trials suggests that adding receptor targets tends to increase the average effect on body weight, at the cost of a shorter and smaller evidence base for the newest molecules. Head-to-head, long-term and safety data remain active areas of study.

For the mechanism behind all three, see the appetite science behind why diets fail and our overview of GLP-1 peptides and weight-loss research.

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