Comparisons
Semaglutide vs Tirzepatide vs Retatrutide: GLP-1 Receptor Agonist Research Comparison
Healthy Aminos Research Team · · 8 min read
Three Generations of Incretin Peptides
The incretin-based peptide landscape has evolved from single-receptor agonists to dual and triple agonists. This article compares the published molecular and clinical data for three compounds: [semaglutide](/peptides/weight-loss/semaglutide), [tirzepatide](/peptides/weight-loss/tirzepatide), and [retatrutide](/peptides/weight-loss/retatrutide).
Molecular Comparison
| Property | Semaglutide | Tirzepatide | Retatrutide | |----------|-------------|-------------|-------------| | Receptor Targets | GLP-1R | GIP-R + GLP-1R | GIP-R + GLP-1R + GCGR | | Amino Acids | 31 | 39 | 39 | | Molecular Weight | 4113.58 Da | 4813.53 Da | 4603.28 Da | | Half-Life Mechanism | C-18 fatty diacid | C-20 fatty diacid | Fatty acid modification | | CAS Number | 910463-68-2 | 2023788-19-2 | 2381089-83-2 |
Published Clinical Trial Data
### Semaglutide
The STEP clinical trial program enrolled over 20,000 participants. [Wilding et al. (2021)](https://pubmed.ncbi.nlm.nih.gov/33567185/) reported the STEP 1 results: a mean weight change of −14.9% versus −2.4% for placebo over 68 weeks (n=1,961). [Garvey et al. (2022)](https://pubmed.ncbi.nlm.nih.gov/36216945/) published STEP 5 two-year data showing −15.2% mean weight change was maintained at 104 weeks.
### Tirzepatide
The SURMOUNT program examined the dual agonist. [Jastreboff et al. (2022)](https://pubmed.ncbi.nlm.nih.gov/35658024/) reported SURMOUNT-1 results: dose-dependent weight reductions of 15.0% (5mg), 19.5% (10mg), and 20.9% (15mg) over 72 weeks. [Aronne et al. (2024)](https://pubmed.ncbi.nlm.nih.gov/38078870/) published SURMOUNT-4 weight maintenance data.
### Retatrutide
The triple agonist is in earlier-stage clinical development. [Jastreboff et al. (2023)](https://pubmed.ncbi.nlm.nih.gov/37366315/) published phase 2 results in the New England Journal of Medicine showing dose-dependent responses up to −24.2% at the 12mg dose over 48 weeks.
Chemical Properties
All three compounds are supplied as lyophilized powders for research. They share the fatty acid albumin-binding strategy for half-life extension but differ in receptor selectivity profiles and sequence length.
*All Healthy Aminos products are for research use only. Not for human or animal consumption. Not FDA approved.*
Research Use Only
FOR RESEARCH USE ONLY. Products sold by Healthy Aminos are intended strictly for in-vitro research and laboratory use. Not for human or animal consumption. Not FDA approved. By purchasing from Healthy Aminos, the buyer acknowledges that these products are not intended to diagnose, treat, cure, or prevent any disease. All products are sold as reference standards and research chemicals only.