Retatrutide vs CagriSema: One Triple Agonist Against a Two-Molecule Combination
Retatrutide is one molecule acting on three receptors (GIP, GLP-1, glucagon); CagriSema is a fixed-dose pairing of two molecules, the amylin analogue cagrilintide and the GLP-1 agonist semaglutide. In separate trials CagriSema reached 22.7% mean weight reduction at 68 weeks (REDEFINE 1, trial-product estimand; 20.4% on the stricter treatment-policy measure) and retatrutide 24.2% at 48 weeks (Phase 2) and 25.0% at 80 weeks (TRIUMPH-1, NEJM 2026). Neither is approved and they have never been compared head-to-head.
No head-to-head results exist. The two programmes differ in population, duration, dose ladder and how the headline figure is calculated (see “Reading the numbers” below). Cross-trial percentages are indicative only. Research context; nothing here is medical or dosing guidance. Regulatory and trial status is as of September 2026.
At a glance
| Retatrutide | CagriSema | |
|---|---|---|
| Composition | One 39-amino-acid peptide | Two molecules, cagrilintide (amylin analogue) and semaglutide (GLP-1 agonist), co-formulated by Novo Nordisk |
| Receptor targets | GIP + GLP-1 + glucagon | Amylin / calcitonin + GLP-1 |
| Developer | Eli Lilly (LY3437943) | Novo Nordisk |
| Cadence | Once-weekly (trials) | Once-weekly |
| Headline data | 24.2% at 48 wk (Phase 2); 25.0% at 80 wk (TRIUMPH-1, 12 mg, NEJM 2026) | 22.7% trial-product / 20.4% treatment-policy at 68 wk (REDEFINE 1) |
| Regulatory position (Sept 2026) | Investigational; Lilly has said it plans an FDA submission in Q1 2027 | FDA new drug application submitted December 2025; not approved |
| Research material at New-U | GLP1-RC-RT (retatrutide reference) | Proprietary Novo Nordisk product; not sold |
One molecule or two
The design choice is the interesting difference. CagriSema reaches its effect by combining two mechanisms that barely overlap: GLP-1 signalling from semaglutide (appetite centres, gastric emptying, glucose-dependent insulin) and amylin signalling from cagrilintide (a separate satiety pathway; preclinical work suggests it may also improve leptin sensitivity). REDEFINE 1 included the combination and each component alone, and reported a larger mean reduction for the combination than for either component.
Retatrutide reaches for breadth inside a single peptide. Its GIP and GLP-1 arms cover the incretin effects; the glucagon arm adds an energy-expenditure lever that neither CagriSema component supplies. One practical consequence is pharmacokinetic: retatrutide is a single compound with a half-life near 6 days, whereas the combination has two components, each with its own profile (semaglutide about 7 days, cagrilintide about 8).
“Two molecules” and “three receptors” are different bets on the same problem, and neither has been shown to beat the other. The more informative question is which pathways a given study is trying to isolate.
Reading the numbers
Headline weight-loss figures depend on how they are counted, and the two programmes do not report the same way.
- Treatment-policy estimand: counts every randomised participant as randomised, including those who stopped treatment. REDEFINE 1 reported 20.4% for CagriSema against 3.0% on placebo.
- Trial-product (efficacy) estimand: estimates the effect if everyone stayed on treatment. The same trial reported 22.7% for CagriSema.
That 2.3-point gap between two honest ways of summarising one trial is comparable to many of the gaps quoted between compounds. Retatrutide’s 24.2% comes from a 338-person Phase 2 trial over 48 weeks; the 25.0% is the peer-reviewed Phase 3 TRIUMPH-1 result for the 12 mg dose at 80 weeks (treatment-regimen estimand, N Engl J Med 2026); the analysis population for each figure is set out in its source. Different sizes, durations and calculations mean the four numbers cannot be lined up as a league table.
| Programme | Population | Duration | Reported mean weight reduction |
|---|---|---|---|
| REDEFINE 1 (CagriSema) | 3,417 adults with overweight/obesity, no diabetes | 68 weeks | 20.4% treatment-policy; 22.7% trial-product |
| Retatrutide Phase 2 | 338 adults with obesity, no diabetes | 48 weeks | 24.2% (12 mg arm) |
| TRIUMPH-1 (retatrutide) | Adults with obesity, no diabetes | 80 weeks | 25.0% (12 mg, NEJM 2026) |
Where each stands
CagriSema is the further along of the two on paper: Novo Nordisk submitted a new drug application to the FDA in December 2025, and the sources reviewed for this page (September 2026) report no marketing authorisation. Retatrutide has reported Phase 3 toplines, and Lilly has said it plans to file in the first quarter of 2027. Approval status matters more than any percentage, because approval reflects a completed safety review that neither compound has yet cleared.
Research access
CagriSema is a proprietary Novo Nordisk co-formulation and is not available as a research reagent; New-U does not sell it. The CagriSema research guide sets out the programme’s published data, and the retatrutide research guide covers the triple agonist.
Research takeaway
- Retatrutide is one three-receptor peptide; CagriSema is two molecules on two pathways.
- The headline figures (22.7% vs 24.2% and 25.0%) come from separate trials and different calculations. They are not a ranking.
- CagriSema’s treatment-policy and trial-product figures differ by 2.3 points; know which one a source is quoting.
- Neither is approved; CagriSema is under FDA review and retatrutide is expected to file in 2027.
Primary sources
- PubMed — Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)
- Novo Nordisk — CagriSema FDA filing announcement
- 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)
- CNBC — Lilly will file for retatrutide approval in 2027
Retatrutide as a research reference (GLP1-RC-RT)
New-U catalogues laboratory research material under GLP1-RC-RT (retatrutide reference). CagriSema is a proprietary Novo Nordisk product and is not sold. 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 CagriSema better than retatrutide?
No trial has compared them, so this cannot be answered from evidence. Separate trials reported 22.7% (REDEFINE 1, trial-product estimand) for CagriSema and 24.2% (Phase 2) and 25.0% (TRIUMPH-1, NEJM 2026) for retatrutide, but populations, durations and calculations differ. Research context only.
What is the difference between retatrutide and CagriSema?
Retatrutide is a single peptide that activates GIP, GLP-1 and glucagon receptors. CagriSema is a fixed-dose combination of two molecules: cagrilintide, an amylin analogue, and semaglutide, a GLP-1 agonist.
Does CagriSema include GIP activity like a tri-agonist?
No. Neither of its two molecules targets the GIP receptor: cagrilintide is an amylin analogue that acts on amylin and calcitonin receptors, and semaglutide is a GLP-1 receptor agonist. Retatrutide is the tri-agonist, activating GIP, GLP-1 and glucagon receptors in one peptide.
Are retatrutide and CagriSema approved?
Neither is approved as of September 2026. Novo Nordisk submitted CagriSema to the FDA in December 2025; Lilly has said it plans to submit retatrutide in the first quarter of 2027.
Why do CagriSema results show two different percentages?
They use different estimands. The treatment-policy figure (20.4%) counts all randomised participants; the trial-product figure (22.7%) estimates the effect if everyone stayed on treatment.
Can CagriSema be bought as a research compound?
No. CagriSema is a proprietary Novo Nordisk co-formulation and New-U does not sell it.
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.