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.*