Retatrutide vs Cagrilintide: Triple Agonist vs Amylin Analogue, Compared
Retatrutide and cagrilintide are not like-for-like alternatives. Retatrutide is an investigational triple agonist of the GIP, GLP-1 and glucagon receptors; cagrilintide is a long-acting analogue of amylin, a different satiety hormone. In separate trials retatrutide reached a 24.2% mean weight reduction at 48 weeks (Phase 2, 12 mg arm) and cagrilintide alone 11.8% at 68 weeks (REDEFINE 1, trial-product estimand). They have never been compared head-to-head, and cagrilintide’s documented research role is as the partner in CagriSema, not as a substitute for an incretin.
No head-to-head results exist. The percentages below come from separate trials with different populations, durations, doses and analysis methods. They are indicative only and are not evidence that either compound outperforms the other. All data is presented for research context; nothing here is medical or dosing guidance. Regulatory and trial status is as of September 2026.
At a glance
| Retatrutide | Cagrilintide | |
|---|---|---|
| Class | Triple GIP / GLP-1 / glucagon receptor agonist | Long-acting amylin analogue |
| Receptor targets | GIP + GLP-1 + glucagon | Amylin (AMY1–3) + calcitonin receptors |
| Developer | Eli Lilly (LY3437943) | Novo Nordisk (AM833) |
| Half-life | ~6 days | ~8 days |
| Documented mean weight reduction | 24.2% at 48 wk (Phase 2, 12 mg arm); 25.0% at 80 wk (TRIUMPH-1, 12 mg, NEJM 2026) | 11.8% at 68 wk (REDEFINE 1, cagrilintide alone, trial-product estimand) |
| Approval | None (investigational) | None as a single agent; CagriSema, the combination with semaglutide, was submitted to the FDA in December 2025 |
| Research material at New-U | GLP1-RC-RT (retatrutide reference) | Cagrilintide |
Two different pathways
The comparison is less about strength than about which signal each molecule supplies.
Retatrutide — three receptors
Activates the GIP, GLP-1 and glucagon receptors. The appetite and glycaemic effects come from the two incretin arms; the glucagon arm adds an energy-expenditure lever. The individual contributions are not yet disentangled in humans.
Cagrilintide — amylin
Amylin is a satiety hormone co-secreted with insulin. Cagrilintide is an acylated, albumin-binding analogue that engages amylin and calcitonin receptors: it lowers hunger signalling (NPY/AgRP down, POMC up), slows gastric emptying and blunts post-meal glucagon. Preclinical work suggests amylin signalling may also improve leptin sensitivity, a separate lever from the incretins.
The two act on different receptor families: retatrutide on the GIP, GLP-1 and glucagon receptors, cagrilintide on amylin and calcitonin receptors. They are different research tools, not interchangeable ones, and the published record reviewed here contains no study of the pair.
What the trials showed
- Retatrutide (Phase 2, NEJM 2023, n=338): dose-dependent mean weight reduction at 48 weeks of 8.7% (1 mg), 17.1% (4 mg), 22.8% (8 mg) and 24.2% (12 mg), against 2.1% on placebo — and the curve had not plateaued. In Phase 3, TRIUMPH-1 (Jastreboff et al., N Engl J Med 2026; PMID 42814954) reported 25.0% at 80 weeks on the 12 mg dose, against 3.9% on placebo.
- Cagrilintide (REDEFINE 1, Phase 3, 68 weeks, n=3,417 adults without diabetes): the trial randomised participants to the CagriSema combination, semaglutide alone, cagrilintide alone or placebo, so the single-agent effect can be read against the combination inside one study:
| REDEFINE 1 arm (68 weeks) | Mean weight reduction, trial-product estimand |
|---|---|
| CagriSema (cagrilintide + semaglutide combination) | 22.7% |
| Semaglutide alone | 16.1% |
| Cagrilintide alone | 11.8% |
In REDEFINE 1, cagrilintide alone reported about half the mean reduction of the combination and less than semaglutide alone; the combination reported the largest mean reduction of the three arms. Pairing with a GLP-1 agonist is the setting in which cagrilintide is being developed.
Is cagrilintide an alternative to retatrutide?
Not on the evidence. The published figures for the two come from different trials with different populations, doses and durations, so they cannot be ranked. What can be said is what each is for in research: retatrutide is a three-receptor agonist under investigation for obesity and related conditions, while cagrilintide is the amylin component, studied on top of a GLP-1 agonist in CagriSema and on its own to isolate amylin signalling.
No trial has tested cagrilintide against retatrutide, and combination research so far has paired cagrilintide with semaglutide, not with a triple agonist. Nothing published supports treating the two as a stack.
Retatrutide alternatives at a glance
Searches for retatrutide alternatives usually mean “what else acts on this pathway, or a neighbouring one”. The alternatives differ along three axes: the receptors they act on (incretin, glucagon, amylin), how often they are given (weekly, monthly, or a daily tablet) and how far each has progressed with regulators. This is the map, with each comparison in its own page.
| Compound | Mechanism | Cadence | Status (Sept 2026) | Comparison |
|---|---|---|---|---|
| Tirzepatide | GIP + GLP-1 (dual) | Weekly | Approved as a medicine in some jurisdictions | Retatrutide vs tirzepatide |
| Semaglutide | GLP-1 | Weekly | Approved as a medicine in some jurisdictions | Retatrutide vs semaglutide |
| CagriSema | Amylin + GLP-1 (two molecules) | Weekly | Submitted to the FDA (Dec 2025) | Retatrutide vs CagriSema |
| MariTide | GLP-1 agonist + GIP antagonist (antibody conjugate) | ~Monthly | Phase 3 | Retatrutide vs MariTide |
| Amycretin | Amylin + GLP-1 (one molecule) | Weekly injection; daily oral | In development | Retatrutide vs amycretin |
| Survodutide | GLP-1 + glucagon (dual) | Weekly | Phase 3 | Retatrutide vs survodutide |
As research compounds
New-U catalogues laboratory research material under GLP1-RC-RT (retatrutide reference) and cagrilintide. Cagrilintide is also the amylin component of CagriSema; the fixed-dose CagriSema product itself is a proprietary Novo Nordisk medicine and is not a research reagent. See the CagriSema research guide for the programme’s published data.
Research takeaway
- Retatrutide acts on the GIP, GLP-1 and glucagon receptors; cagrilintide on amylin and calcitonin receptors. They are different research tools.
- The figures come from different trials and cannot be ranked; within REDEFINE 1, cagrilintide alone reported about half of CagriSema’s mean reduction.
- Cagrilintide’s studied role is as a partner to a GLP-1 agonist, not as a replacement for an incretin.
- Neither is approved as a single agent, and no head-to-head results exist.
Primary sources
- New England Journal of Medicine — Triple–Hormone-Receptor Agonist Retatrutide for Obesity (Jastreboff et al., 2023)
- New England Journal of Medicine — Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (Jastreboff et al., 2026; TRIUMPH-1)
- PubMed — Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)
Retatrutide as a research reference (GLP1-RC-RT)
New-U catalogues laboratory research material under GLP1-RC-RT (retatrutide reference) and cagrilintide. The trial results above describe the sponsors’ investigational products, not this material. Published Certificates of Analysis are available for the batches listed in the COA library. Research use only – all claims made on this site are for testing and research use only.
View GLP1-RC-RTFrequently asked questions
Is cagrilintide an alternative to retatrutide?
Not on the evidence. Cagrilintide acts on amylin and calcitonin receptors, a different pathway from retatrutide’s GIP, GLP-1 and glucagon receptors, and it has been studied mainly as the amylin partner in CagriSema. No trial compares the two. Research context only.
How do the published results for retatrutide and cagrilintide compare?
In separate trials retatrutide reported a 24.2% mean weight reduction at 48 weeks (Phase 2, 12 mg arm) and cagrilintide alone 11.8% at 68 weeks (REDEFINE 1, trial-product estimand). Different designs and populations mean the figures cannot be ranked. Research context, not a recommendation.
Can retatrutide and cagrilintide be combined?
No published trial tests the pair. Combination research so far has paired cagrilintide with semaglutide (CagriSema). Nothing in the literature supports treating retatrutide and cagrilintide as a stack.
How do the mechanisms differ?
Retatrutide is a triple agonist of the GIP, GLP-1 and glucagon receptors. Cagrilintide is a long-acting amylin analogue acting on amylin and calcitonin receptors, a satiety pathway separate from the incretins.
Are both available as research compounds?
Yes. New-U catalogues laboratory research material under GLP1-RC-RT (retatrutide reference) and cagrilintide, for laboratory research use only. Published Certificates of Analysis are available for the batches listed in the COA library.
External links are provided for research reference only; New-U is not affiliated with the cited organisations. All figures are published trial results shown for research context, not dosing guidance. New-U Research Compounds supplies research compounds strictly for laboratory research use only — not for human consumption.