Retatrutide vs Cagrilintide (2026): Triple Agonist vs Amylin Analogue Trial Data Compared
Retatrutide vs cagrilintide: 28.3% weight loss at 80 weeks in TRIUMPH-1 vs 20.4% for CagriSema in REDEFINE 1. See how the two programs compare in 2026.
Research reference only. The information in this article is a summary of peer-reviewed scientific literature. It does not constitute medical advice and is not intended to guide human use. See our full disclaimer.
Retatrutide vs cagrilintide is a comparison between two once-weekly injectable peptides that reduce body weight through different receptor systems: retatrutide is a triple agonist of the GIP, GLP-1 and glucagon receptors, while cagrilintide is a long-acting amylin analogue studied mostly inside the CagriSema combination. This page summarizes the published trial data for each compound, and flags where the numbers cannot be compared directly.
Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.
Quick Answer: Retatrutide reported a 28.3% mean weight reduction at 80 weeks at 12 mg in the Phase 3 TRIUMPH-1 trial, while cagrilintide has been studied mainly as CagriSema, which reported 20.4% at 68 weeks in REDEFINE 1 (PMID 40544433). The compounds act on different receptors and were studied in separate trials, so the figures are descriptive only.
TL;DR:
- Retatrutide targets three receptors (GIPR, GLP-1R, GCGR); cagrilintide targets amylin receptors (AMY1R, AMY2R, AMY3R)
- Retatrutide: Phase 3 TRIUMPH program from Eli Lilly, with a Biologics License Application planned for Q1 2027
- Cagrilintide: evidence comes largely from CagriSema (cagrilintide plus semaglutide), with Phase 3 REDEFINE 1 published in 2025
- Cagrilintide monotherapy and CagriSema are different arms and should not be conflated
- No head-to-head trial exists between the two
| Parameter | Retatrutide | Cagrilintide |
|---|---|---|
| Target | GIPR / GLP-1R / GCGR triple agonist | Amylin receptor agonist (AMY1R, AMY2R, AMY3R) |
| Developer | Eli Lilly | Novo Nordisk |
| Most advanced stage | Phase 3 (TRIUMPH program) completed readouts | Phase 3 (REDEFINE) as CagriSema; NDA submitted December 2025 |
| Lead evidence | TRIUMPH-1: -28.3% at 80 weeks (12 mg, efficacy estimand) | REDEFINE 1: CagriSema -20.4% at 68 weeks |
| Dosing interval | Once weekly, subcutaneous | Once weekly, subcutaneous |
| Regulatory status | Investigational | Investigational |
Retatrutide: mechanism and evidence base
Retatrutide (LY3437943) is a single peptide that activates the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor and the glucagon receptor. In the published framing, GLP-1R and GIPR signalling are associated with appetite suppression and insulin secretion, while glucagon receptor signalling is associated with increased energy expenditure and hepatic fat oxidation.
A 2026 Molecular Metabolism study (PMID 41997446) examined this in rodents. Retatrutide normalized body weight in obese GLP-1R knock-out mice, and a GIPR:GCGR co-agonist lacking GLP-1 activity reduced excess body weight to a similar degree in diet-induced obese mice and rats. This is preclinical mechanism context, and it does not predict human outcomes.
In humans, the Phase 2 obesity trial published in the New England Journal of Medicine in 2023 (PMID 37366315) randomised 338 adults to retatrutide 1 mg to 12 mg or placebo. At 48 weeks, the 12 mg group reported -24.2% mean body weight change versus -2.1% for placebo. The Phase 3 TRIUMPH-1 trial (NCT05929066) enrolled 2,339 adults with obesity or overweight and no diabetes, and the sponsor reported -28.3% at 80 weeks for the 12 mg arm under the efficacy estimand, versus -2.2% for placebo. The treatment-regimen estimand for the same arm was -25.0%, so published coverage quoting either figure refers to the same trial.
Cagrilintide: mechanism and evidence base
Cagrilintide is a long-acting synthetic amylin analogue. Amylin is co-secreted with insulin from pancreatic beta cells, and cagrilintide binds heteromeric complexes of the calcitonin receptor and receptor activity-modifying proteins. Receptor activation engages hypothalamic (homeostatic) and mesolimbic (hedonic) satiety pathways. A C20 fatty acid chain supports albumin binding and a half-life of roughly 159 to 195 hours in published pharmacokinetic work.
Most cagrilintide evidence comes from combination studies with semaglutide. In Phase 3 REDEFINE 1 (PMID 40544433), once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg (CagriSema) produced a 20.4% mean weight reduction at 68 weeks versus 3.0% with placebo, and 60% of participants reached at least 20% weight loss. Cagrilintide monotherapy was a separate arm in that trial and reported a smaller reduction of 11.8% at 68 weeks. A Phase 2 dose-finding trial (PMID 34798060) reported 10.8% at 26 weeks for the 4.5 mg dose, versus 3.0% for placebo.
Side-by-side: two routes to satiety
The two compounds illustrate different pharmacological strategies. Retatrutide combines three peripheral and central metabolic receptor signals in one molecule. Cagrilintide adds a distinct, largely central satiety axis that can be layered onto an existing incretin. The comparison therefore depends on which cagrilintide arm is used as the reference.
| Comparison point | Retatrutide 12 mg | Cagrilintide monotherapy | CagriSema |
|---|---|---|---|
| Trial | TRIUMPH-1 (80 weeks) | REDEFINE 1 arm (68 weeks) | REDEFINE 1 (68 weeks) |
| Mean weight change | -28.3% (efficacy estimand) | -11.8% | -20.4% |
| Placebo | -2.2% | -3.0% | -3.0% |
| Receptor systems | Incretin plus glucagon | Amylin | Amylin plus GLP-1 |
Differences in estimands, duration, populations and dose escalation schedules mean these columns cannot be ranked against each other. The tirzepatide literature is often used as a common reference point, and the half-life chart allows dosing intervals for the incretin and amylin compounds to be viewed together.
How to read the numbers
Three points limit cross-trial reading. First, estimands differ: the efficacy estimand assumes participants stayed on treatment, while the treatment-regimen estimand counts everyone randomised, so a single arm can be quoted at two values (for retatrutide 12 mg, -28.3% and -25.0%). Second, duration differs, with 80 weeks in TRIUMPH-1 and 68 weeks in REDEFINE 1, and weight curves had not fully plateaued in either. Third, baseline characteristics and dose-escalation schedules differ between programs. For these reasons, researchers typically describe the two programs in parallel rather than as a ranking, and treat the amylin and incretin-glucagon approaches as mechanistically complementary questions.
Differential research applications
Researchers studying glucagon-mediated energy expenditure and hepatic effects have used retatrutide as a tool for triple-receptor questions. Researchers studying amylin pharmacology have used cagrilintide to test whether a distinct satiety axis adds to incretin effects, and the ongoing amylin pipeline gives context: see eloralintide vs cagrilintide and petrelintide vs cagrilintide. The trial tracker lists registered trials for both programs.
Regulatory status
Retatrutide is investigational, and the sponsor has stated it plans a Biologics License Application in Q1 2027. Cagrilintide has no approval as a standalone agent. A New Drug Application for CagriSema was submitted to the FDA in December 2025 and is under review. Neither compound is approved for human or veterinary use in the context of this page, and research-grade material is not a substitute for an approved product.
Cited studies
- PMID 37366315, "Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial" (New England Journal of Medicine, 2023). https://doi.org/10.1056/NEJMoa2301972
- PMID 41997446, "GIPR:GCGR co-agonism restores normal weight in obese rodents." (Molecular Metabolism, 2026). https://doi.org/10.1016/j.molmet.2026.102365
- PMID 40544433, "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)." (New England Journal of Medicine, 2025). https://doi.org/10.1056/NEJMoa2502081
- PMID 34798060 · Phase 2 cagrilintide dose-finding trial (The Lancet, 2021).
Frequently asked questions
Q: What is the difference between retatrutide and cagrilintide?
A: Retatrutide is a triple agonist of the GIP, GLP-1 and glucagon receptors, while cagrilintide is an amylin analogue. They act on different receptor systems and are developed by different companies.
Q: Cagrilintide vs retatrutide: which showed more weight loss in trials?
A: Retatrutide 12 mg reported 28.3% at 80 weeks in TRIUMPH-1, while cagrilintide monotherapy reported 11.8% and CagriSema 20.4% at 68 weeks in REDEFINE 1. The trials differ in design and duration, and no head-to-head study exists.
Q: Is cagrilintide the same as CagriSema?
A: No. Cagrilintide is the amylin analogue alone, while CagriSema is a combination of cagrilintide and semaglutide. Most published efficacy data refer to the combination.
Q: Has retatrutide been studied with an amylin analogue?
A: The published trials cited here evaluated retatrutide on its own. Any combination data would need to be confirmed in the registered trial listings.
Q: Are retatrutide and cagrilintide approved?
A: Neither is approved as a standalone agent. Retatrutide remains investigational with a BLA planned for 2027, and CagriSema has a pending NDA submission.
See also:
- Eloralintide vs cagrilintide: compares cagrilintide with a selective amylin agonist
- Retatrutide vs tirzepatide: triple versus dual incretin agonism
- Petrelintide vs cagrilintide: two long-acting amylin analogues
For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.