Semaglutide, tirzepatide and retatrutide are the three most-studied incretin analogues in current metabolic research. They are often discussed as if they were versions of the same thing at different strengths. They are not — they engage different numbers of receptors, and that difference is the entire point of comparing them.
The short version
Count the receptors. Semaglutide is a single agonist, tirzepatide a dual agonist, retatrutide a triple agonist. Each generation adds a pathway rather than more of the same one, which is why the research literature treats them as distinct tools rather than as a potency ladder.
Side by side
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Class | GLP-1 receptor agonist | GIP / GLP-1 dual agonist | GIP / GLP-1 / glucagon triple agonist |
| Receptors engaged | 1 | 2 | 3 |
| Development code | NN9535 | LY3298176 | LY3437943 |
| Structural basis | Modified GLP-1 backbone with a fatty-acid chain for albumin binding | GIP-based backbone engineered for activity at both receptors | GIP-based backbone extended to add glucagon-receptor activity |
| Primary research focus | Glucose regulation and gastric emptying in metabolic models | Combined incretin signalling; frequently compared against single agonists | Energy expenditure via the added glucagon arm, alongside incretin signalling |
| Position in the literature | The most published of the three; the usual comparator | Extensively published; the current benchmark for dual agonism | Newest and least published; an active area rather than a settled one |
| Sizes we stock | 5mg, 10mg | 10mg, 15mg, 30mg, 40mg | 5mg, 10mg, 20mg, 30mg |
| Measured purity, current lot | 99.89% (5 mg) | 99.94% (30 mg) | 99.83% (5 mg), 99.95% (10 mg), 99.86% (30 mg) |
Purity figures are from the published certificate for the lot currently in stock — read the certificates. Current pricing for every size is on the price list.
What each receptor actually does
GLP-1. The glucagon-like peptide-1 receptor is the pathway all three share. In research models it is studied for glucose-dependent insulin release, gastric emptying and satiety signalling. Semaglutide engages this and nothing else.
GIP. Glucose-dependent insulinotropic polypeptide is a second incretin receptor. Adding it is what separates tirzepatide from semaglutide, and much of the comparative literature exists to isolate what that second pathway contributes. See tirzepatide vs semaglutide.
Glucagon. The third receptor is the one that makes retatrutide structurally different rather than incrementally stronger. Glucagon-receptor activity is studied in the context of energy expenditure — a different mechanism from the appetite and glucose-handling pathways the other two work through. See retatrutide vs tirzepatide.
Which is appropriate for a given study
That depends entirely on the question being asked, and it is a design decision rather than a ranking. A protocol isolating GLP-1 signalling wants the single agonist, because adding pathways adds confounders. Work on combined incretin effects wants the dual. Research reaching specifically at the glucagon arm wants the triple. “Newest” is not a synonym for “most appropriate” — semaglutide remains the most-published of the three, which for comparative work is often the point.
One practical consideration: retatrutide is the newest and has the thinnest body of independent literature behind it, so results are correspondingly harder to contextualise against prior work.
Handling
All three ship lyophilized and are reconstituted identically with bacteriostatic water — add slowly down the vial wall, swirl rather than shake. Final concentration follows from the volume added; the reconstitution calculator does the arithmetic, and the reconstitution guide covers the procedure. Store lyophilized vials at −20°C (−4°F), protected from light, and refrigerate once in solution — see the storage guide.
Shop the compounds
- Buy research-grade semaglutide — single GLP-1 agonist.
- Buy research-grade tirzepatide — GIP/GLP-1 dual agonist.
- Buy research-grade retatrutide — GIP/GLP-1/glucagon triple agonist.
- Cagrilintide and the cagrilintide + semaglutide blend work through the amylin pathway instead, and are often studied alongside these three.
For the wider class, see the GLP-1 and metabolic research peptides guide.
Common questions
What is the difference between retatrutide, tirzepatide and semaglutide?
How many receptors each one engages. Semaglutide is a single GLP-1 receptor agonist. Tirzepatide is a dual agonist, adding the GIP receptor. Retatrutide is a triple agonist, adding glucagon-receptor activity on top of both. Each adds a distinct pathway rather than more of the same one, so in research they are treated as different tools rather than as stronger versions of each other.
Is retatrutide stronger than tirzepatide?
That framing does not really apply. Retatrutide engages a third receptor — glucagon — that tirzepatide does not, so it acts through an additional mechanism rather than acting more intensely through the same ones. Which is appropriate depends on the pathway a study is designed to isolate.
Which one has the most research behind it?
Semaglutide, by a wide margin — it is the oldest of the three and the usual comparator in the literature. Tirzepatide is extensively published as the dual-agonist benchmark. Retatrutide is the newest and has the thinnest independent literature, which makes its results harder to contextualise against prior work.
Can I see purity results for all three?
Yes. Every lot is tested by Freedom Diagnostics, an independent US laboratory, by HPLC-UV for purity and LC-MS for identity, and every certificate is published on the site as a free download — including the raw chromatogram and lot number. The measured figure for each compound is in the comparison table above.
Are they reconstituted differently?
No. All three ship lyophilized and are reconstituted the same way, with bacteriostatic water added slowly down the vial wall and swirled rather than shaken. The final concentration depends on the volume added, not on which compound it is.
Research use only. All compounds discussed are supplied strictly for laboratory research. They are not drugs, foods, cosmetics or medical devices, are not for human or veterinary use, and nothing above describes dosing, therapeutic use or clinical outcomes. Mechanisms are described as studied in preclinical and laboratory research.
