Tirzepatide vs Semaglutide vs Retatrutide.
All three are incretin-class research peptides studied in metabolic-disease and obesity research. They differ in receptor selectivity, half-life, mechanism, and the magnitude of effect observed in published rodent and human studies. This page is for qualified researchers comparing molecules for laboratory programs — it is not a recommendation for therapeutic use.
| Tirzepatide | Semaglutide | Retatrutide | |
|---|---|---|---|
| Class | Dual GIP/GLP-1 agonist | GLP-1 mono-agonist | Triple GIP/GLP-1/GCGR agonist |
| Length | 39 residues (C20 diacid lipidated) | 31 residues (C18 diacid lipidated) | 39 residues (C20 diacid lipidated, glucagon-derived) |
| Molecular weight | 4,813.5 Da | 4,113.5 Da | 4,731.4 Da |
| Receptor selectivity | GIPR + GLP-1R (dual) | GLP-1R (selective mono) | GIPR + GLP-1R + GCGR (triple) |
| Half-life (human plasma) | ~120 hours | ~165 hours (longest) | ~144 hours |
| Dosing frequency in trials | Once weekly (SC) | Once weekly (SC or PO oral) | Once weekly (SC) |
| HbA1c reduction (trial) | −1.5% to −2.3% (SURPASS) | −1.4% to −1.8% (SUSTAIN) | −1.5% to −2.0% (TRIUMPH) |
| Body weight reduction (trial) | −12% to −21% (SURMOUNT) | −6% to −15% (STEP) | −12% to −24% (TRIUMPH) |
| Primary research applications | Dual-incretin pharmacology, β-cell proliferation, hepatic steatosis models, comparative incretin studies | GLP-1R signaling, β-cell insulin-secretion assays, hypothalamic feeding circuits, GLP-1R internalisation | Triple-incretin pharmacology, energy expenditure, hepatic lipid oxidation, class-B GPCR signalling |
| Cardiovascular signal | MACE reduction in T2DM (SURPASS-CVOT) | MACE reduction in T2DM (SUSTAIN-6, SELECT) | Heart rate ↑ in clinical data; long-term CV outcomes pending |
| Most common adverse signals in trial literature | Nausea, vomiting, transient appetite suppression | Nausea, vomiting, GI slowing | Nausea, vomiting, increased heart rate at higher doses |
| Helix SKU | HX-TR series | HX-SM series | HX-RT series |
| Pack sizes | 5 / 10 / 15 / 20 mg × 10 vials | 5 / 10 / 30 mg × 10 vials | 5 / 10 / 20 mg × 10 vials |
| Starting price (USD) | $64 / 5 mg pack | $168 / 5 mg pack | $76 / 5 mg pack |
How researchers choose between them
| If your lab needs… | Best fit |
|---|---|
| Reference GLP-1 mono-agonist for receptor signalling | Semaglutide |
| Dual-incretin pharmacology without glucagon activity | Tirzepatide |
| Energy-expenditure / hepatic lipid-oxidation readouts | Retatrutide |
| Comparative pharmacology across incretin classes | All three (matched DIO studies) |
| Established reference with extensive prior literature | Semaglutide (most published data) |
| Best published effect size in obesity/NASH models | Retatrutide |
| Best receptor selectivity (clean pharmacology) | Semaglutide |
| Best value per mg at research scale | Tirzepatide 5 mg ($64) |
Methodology & sources
All clinical numbers above are drawn from the published peer-reviewed primary literature indexed in PubMed. The semi-quantitative HbA1c and weight-reduction ranges are pulled from the SURPASS, SUSTAIN, STEP, SURMOUNT, and TRIUMPH trial programmes, with effect sizes stratified by dose and patient population. Mechanism details are drawn from the original discovery papers and pharmacology reviews.