Anyone lining up the newest research compounds around weight regulation sees two families that are often lumped together. Cagrilintide and eloralintide act on the amylin receptor. Tirzepatide and retatrutide act on the incretin receptors. These are different hormone systems, with different trial designs, different outcomes and a striking difference in reported tolerability.
This page places the four compounds side by side on the basis of published research and manufacturer press releases. Peplife supplies these compounds strictly as Research Use Only for laboratory research. Nothing below is dosing advice or medical information.
Two hormone systems, two routes
Amylin is a hormone that the beta cells of the pancreas release alongside insulin after a meal. It acts mainly on the area postrema in the brainstem, slows gastric emptying and suppresses glucagon release. Amylin analogues mimic that signal and bind to the amylin receptor, and depending on the compound also to calcitonin receptors.
Incretins are gut hormones. GLP-1 and GIP are released from the intestinal wall after a meal and amplify glucose-dependent insulin secretion, while GLP-1 additionally suppresses appetite centrally. Tirzepatide acts on GLP-1 and GIP at the same time. Retatrutide adds the glucagon receptor to that, which affects energy expenditure as well as appetite.
The core difference lies in the point of action. The amylin route mainly drives satiety without triggering the full incretin cascade. In the studies published so far, reported gastrointestinal complaints on the amylin route are accordingly lower than with the strongest incretin combinations.
The four compounds in a table
| Substance | Route | Receptors | Most advanced public data | Reported change in body weight |
|---|---|---|---|---|
| Cagrilintide | Amylin | Amylin and calcitonin receptors | Phase 2, 26 weeks, 2.4 mg (The Lancet, 2021) | minus 10.8 percent, placebo minus 3.0 percent |
| Eloralintide (LY3841136) | Amylin, selective | Amylin receptor | Phase 2, 48 weeks, multiple arms (November 2025) | minus 9.5 to minus 20.1 percent, placebo minus 0.4 percent |
| Tirzepatide | Incretin, dual | GLP-1 and GIP | Phase 3 SURMOUNT-1, 72 weeks (NEJM, 2022) | minus 16.0 to minus 22.5 percent, placebo minus 2.4 percent |
| Retatrutide | Incretin, triple | GLP-1, GIP and glucagon | Phase 3 TRIUMPH-4, 68 weeks (December 2025) | minus 26.4 to minus 28.7 percent, placebo minus 2.1 percent |
These figures come from different studies with different durations, populations and endpoints. They are not directly comparable. The table shows what has been publicly reported per compound, not the outcome of a head-to-head trial.
Cagrilintide vs tirzepatide
These two are set against each other most often, because both mark the step beyond the classic mono-agonist. The comparison only looks lopsided as long as you ignore trial duration. Cagrilintide was studied as a single compound over 26 weeks, tirzepatide over 72 weeks. A large part of the difference in reported weight change is duration, not mechanism.
More importantly, cagrilintide is barely studied as a single compound any more. The development programme shifted to the fixed combination with semaglutide. In that combination a mean weight change of minus 22.7 percent was reported over 68 weeks, comparable to the highest tirzepatide arm, but reached through two mechanisms instead of one.
For laboratory research that means a practical difference. Cagrilintide mostly appears as the amylin component within a combination or blend, tirzepatide almost always as a standalone dual agonist.
Eloralintide vs retatrutide
This is the sharpest contrast in the comparison: a selective amylin receptor agonist against a triple incretin agonist. In the phase 2 study over 48 weeks eloralintide reached a maximum of minus 20.1 percent. In the phase 3 study TRIUMPH-4 over 68 weeks retatrutide reached minus 28.7 percent at the highest dose.
The flip side is in the safety data. In the highest arm retatrutide showed nausea in more than four out of ten participants and almost one in five discontinued because of adverse events. For eloralintide the manufacturer reported that the incidence of gastrointestinal complaints and fatigue at the two lowest doses was at placebo level and that slower titration lowered the incidence further.
So the question is not which compound is stronger. The question is how much tolerability is given up for how much effect, and that is exactly the axis on which these two classes differ.
Tolerability: where the difference lies
| Study arm | Nausea | Vomiting | Discontinuation due to adverse events |
|---|---|---|---|
| Tirzepatide 15 mg (SURMOUNT-1) | 31.0 percent | 12.2 percent | 6.2 percent |
| Placebo (SURMOUNT-1) | 9.5 percent | 1.7 percent | 2.6 percent |
| Retatrutide 9 mg (TRIUMPH-4) | 38.1 percent | 20.4 percent | 12.2 percent |
| Retatrutide 12 mg (TRIUMPH-4) | 43.2 percent | 20.9 percent | 18.2 percent |
| Placebo (TRIUMPH-4) | 10.7 percent | 0.0 percent | 4.0 percent |
For eloralintide the percentages per dose have not yet been published in the same form. The manufacturer reported gastrointestinal complaints and fatigue as the most common adverse events, with an incidence at placebo level at the two lowest doses. For cagrilintide as a single compound the same caveat applies: the phase 2 publication uses a different reporting format than the phase 3 programmes above.
Why the two routes are being combined
The most interesting development is not that the classes compete, but that they are being stacked. CagriSema combines cagrilintide with semaglutide in a fixed ratio and reported a mean weight change of minus 22.7 percent over 68 weeks in REDEFINE-1.
Novo Nordisk is additionally studying amycretin, a molecule that unites amylin and GLP-1 activity in a single compound. Zealand Pharma and Roche are studying petrelintide, a long-acting amylin analogue that was tested over 42 weeks in the phase 2 study ZUPREME-1 and for which phase 3 is planned for the second half of 2026. Roche also wants to combine petrelintide with CT-388, a dual GLP-1 and GIP agonist.
The underlying idea is always the same. The incretin route delivers the largest weight change but also the most gastrointestinal complaints. The amylin route delivers satiety with a more favourable adverse event profile. By combining the two, researchers hope to decouple effect from tolerability.
What this means for laboratory research
All four compounds in this comparison are lyophilised peptides that are reconstituted before use in the laboratory. Because the classes have different molecular masses and are described in different units in the literature, it is important to note per compound which concentration is in the vial after reconstitution.
With combinations and blends there is an extra calculation step. A vial with several components yields a different amount per component than the total weight suggests. The Peplife reconstitution guide includes a calculator with a blend mode that works out how many milligrams of each constituent are in a given volume.
For newer compounds such as eloralintide, identity verification matters more than with established peptides. Ask for a certificate of analysis per batch with HPLC purity and mass spectrometry, and check that the stated molecular weight matches the published structure.
Interested in eloralintide, petrelintide or amycretin?
These compounds are not part of our standard range. Supply can still be discussed on request, subject to availability and to identity verification on the batch. Tell us briefly what your research requires and we will come back to you on what is possible.
Frequently asked questions
What is the difference between an amylin analogue and a GLP-1 agonist?
An amylin analogue mimics the hormone amylin and acts through the amylin receptor, with satiety via the brainstem as its main route. A GLP-1 agonist mimics a gut hormone and acts through the GLP-1 receptor, with appetite suppression and glucose-dependent insulin secretion. They are two different hormone systems that in research are steered towards the same outcome.
Is cagrilintide the same as CagriSema?
No. Cagrilintide is the standalone amylin analogue. CagriSema is the fixed combination of cagrilintide with semaglutide. The reported outcomes of the two differ considerably, because CagriSema combines two mechanisms and was studied over a longer period.
Why does retatrutide score higher than eloralintide in the studies?
Retatrutide acts on three receptors at once, including the glucagon receptor that influences energy expenditure. In addition, the phase 3 study of retatrutide ran 68 weeks against 48 weeks for the phase 2 study of eloralintide. Both factors contribute to the difference in reported outcome.
Which compound causes the fewest gastrointestinal complaints?
On the basis of the reports available now, the amylin route looks more favourable than the strongest incretin combinations. At the two lowest eloralintide doses the incidence of gastrointestinal complaints was at placebo level, whereas retatrutide in the highest arm showed nausea in more than four out of ten participants. No head-to-head trial between these compounds has been published.
Can amylin and incretin peptides be in one blend?
In clinical research they are indeed combined, as in CagriSema. In laboratory research the study protocol determines whether compounds are dissolved separately or together. Peplife gives no protocol or dosing advice on this and supplies strictly as Research Use Only.
Are these compounds approved?
Of the four compounds in this comparison, only tirzepatide is approved as a medicine. Cagrilintide, eloralintide and retatrutide are research compounds without marketing authorisation for weight management. Peplife supplies them strictly as Research Use Only for laboratory research, not for use in humans or animals.
Related research · RUO
Eloralintide and the amylin agonists · Cagrilintide research · CagriSema research · Tirzepatide research · Retatrutide research · Comparing GLP-1 peptides: mono, dual and triple · Retatrutide vs tirzepatide vs semaglutide · GLP-1: the next generation · Reconstitution guide with blend calculator
Sources
The Lancet — Eloralintide, a selective amylin receptor agonist, phase 2 · Eli Lilly — press release phase 2 results eloralintide, 6 November 2025 · Eli Lilly — TRIUMPH-4 phase 3 results retatrutide, 11 December 2025 · Eli Lilly — SURMOUNT-1 published in NEJM · NEJM — Tirzepatide Once Weekly for the Treatment of Obesity · The Lancet — Once-weekly cagrilintide for weight management, phase 2 · Novo Nordisk — REDEFINE-1 CagriSema, published in NEJM · Zealand Pharma — pipeline petrelintide
Disclaimer
This article discusses scientific research and is informational only. The compounds mentioned are supplied by Peplife strictly as Research Use Only (RUO) for laboratory research. Nothing here is medical, diagnostic, or dosing advice. Named medicines are cited only to discuss published research.