Eloralintide vs Amycretin (2026): Selective Amylin vs Unimolecular Amylin/GLP-1 Agonist Data
Eloralintide hit up to 20% weight loss at 48 weeks; amycretin 22-24% at 36 weeks. Compare mechanisms, Phase 3 status, dosing and developers side by side.
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Eloralintide vs amycretin is the clearest head-to-head in next-generation amylin research: Eli Lilly's eloralintide activates the amylin receptor alone, while Novo Nordisk's amycretin (now also called zenagamtide) is a single molecule that activates both the amylin and GLP-1 receptors. Both are once-weekly subcutaneous peptides in Phase 3 development as of October 2026, and both have produced roughly 20% or greater mean weight reduction in published mid-stage trials, but they got there through different pharmacology and very different trial designs.
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Quick Answer: Eloralintide is a selective amylin receptor agonist (single mechanism) that reported up to about 20% mean weight reduction at 48 weeks in a 263-person Phase 2 trial, while amycretin is a unimolecular amylin plus GLP-1 receptor co-agonist (dual mechanism) that reported 22.0% to 24.3% at 36 weeks in a 125-person Phase 1b/2a study. Both are investigational and neither has been compared directly in the same trial.
TL;DR:
- Eloralintide (Lilly) targets the amylin receptor only; amycretin (Novo Nordisk) targets amylin and GLP-1 receptors in one molecule.
- Eloralintide Phase 2: 9% to 20% mean weight reduction at 48 weeks vs 0.4% with placebo (Lancet, 2025).
- Amycretin Phase 1b/2a: 22.0% (20 mg) and 24.3% (60 mg) at 36 weeks vs placebo; Phase 2 type 2 diabetes data published in 2026.
- Eloralintide is being developed both alone and as an add-on to tirzepatide; amycretin is designed to replace a two-drug combination.
- Both are investigational, not FDA approved, and not eligible for 503A compounding.
Eloralintide vs amycretin at a glance
| Feature | Eloralintide | Amycretin (zenagamtide) |
|---|---|---|
| Developer | Eli Lilly | Novo Nordisk |
| Receptor targets | Amylin receptor (selective) | Amylin receptor + GLP-1 receptor |
| Molecular design | Single-target peptide | Unimolecular co-agonist |
| Most advanced stage | Phase 3 | Phase 3 |
| Key weight-loss figure | Up to ~20% at 48 weeks (Phase 2, n=263) | 22.0% to 24.3% at 36 weeks (Phase 1b/2a, n=125) |
| Dosing interval studied | Once weekly, subcutaneous | Once weekly subcutaneous; once-daily oral also studied |
| Combination strategy | Add-on to tirzepatide (EloraTZP) | Built-in GLP-1 activity |
The headline numbers are not directly comparable. The eloralintide figure comes from a larger, longer, multicentre Phase 2 trial, while the amycretin figure comes from a smaller single-site study with separate dose-escalation parts. Cross-trial comparison is indirect.
Eloralintide: mechanism and evidence base
Eloralintide (LY3841136) is a long-acting peptide agonist of the amylin receptor. Amylin is a hormone co-secreted with insulin by pancreatic beta cells. It acts on the area postrema and brainstem to reduce meal size, slow gastric emptying and suppress post-meal glucagon. The amylin receptor is a heterodimer of the calcitonin receptor and a receptor activity-modifying protein (RAMP). Eloralintide was designed to favour amylin receptor signalling over the calcitonin receptor alone, which distinguishes it from the dual amylin and calcitonin receptor agonist cagrilintide.
Because eloralintide does not engage the GLP-1 or GIP receptors, researchers describe it as GLP-1-independent. That makes it a candidate both for monotherapy and for layering on top of incretin agonists such as tirzepatide.
The primary evidence is a 48-week, multicentre, double-blind, placebo-controlled Phase 2 trial published in The Lancet (PMID 41207310; NCT06230523). It randomised 263 adults with obesity or overweight and at least one weight-related comorbidity, without type 2 diabetes, across six dose and titration arms (1 mg to 9 mg) or placebo. Mean body-weight reduction ranged from roughly 9% to 20% across arms versus 0.4% with placebo. Gastrointestinal events and fatigue were the most commonly reported adverse events, and they were dose-related.
Lilly has since started several Phase 3 trials, including NCT07282600 (obesity with type 2 diabetes), NCT07369011 (obstructive sleep apnea) and ENLIGHTEN-6 (NCT07392190, add-on to a weekly incretin). In September 2026 Lilly also reported Phase 2b results for EloraTZP, the eloralintide plus tirzepatide combination, in adults with type 2 diabetes.
Amycretin: mechanism and evidence base
Amycretin is a first-in-class unimolecular agonist of both the GLP-1 receptor and the amylin receptor. Instead of co-administering two peptides, as in CagriSema (cagrilintide with semaglutide), amycretin places both activities in one molecule. Its later-stage development name is zenagamtide.
The rationale is that GLP-1 and amylin reduce food intake through partly separate brainstem and hypothalamic circuits, so engaging both can add to the effect. GLP-1 receptor activity also brings glucose-dependent insulin secretion, which is relevant for type 2 diabetes research.
The subcutaneous Phase 1b/2a study was published in The Lancet in June 2025 (DOI 10.1016/S0140-6736(25)01185-7). It randomised 125 adults with overweight or obesity to amycretin (n=101) or placebo (n=24) across several parts. At week 36, mean body-weight change was -22.0% with 20 mg versus +1.9% with placebo, and -24.3% with 60 mg versus -1.1% with placebo. The safety and tolerability profile was described as consistent with other GLP-1 and amylin agonists, with gastrointestinal events most common.
In 2026 two companion Phase 2 trials in type 2 diabetes were published in The Lancet. The once-weekly subcutaneous trial (PMID 42532080; 262 participants) reported HbA1c reductions of 0.9 to 1.7 percentage points at 36 weeks. The once-daily oral trial (PMID 42532079; 186 participants) reported HbA1c reductions of 0.9 to 1.4 points, with up to 10.3% weight reduction at the 25 mg dose. Novo Nordisk started a Phase 3 obesity programme in 2026.
Side-by-side comparison
| Parameter | Eloralintide | Amycretin |
|---|---|---|
| Mechanism class | Selective amylin receptor agonist | GLP-1 + amylin receptor co-agonist |
| GLP-1 receptor activity | None | Yes |
| Route | Subcutaneous | Subcutaneous and oral |
| Dosing interval | Once weekly | Once weekly (SC); once daily (oral) |
| Largest published trial | Phase 2, n=263, 48 weeks | Phase 2 T2D, n=262, 36 weeks |
| Obesity trial population | Without type 2 diabetes | Overweight or obesity, single US site |
| Regulatory status (Oct 2026) | Investigational, Phase 3 | Investigational, Phase 3 |
| Primary research applications | Amylin-only satiety signalling, incretin add-on | Single-molecule dual agonism, oral peptide delivery |
Half-life data for both peptides support once-weekly dosing. The half-life chart shows where these sit next to other incretin and amylin analogues.
Differential research applications
The choice between the two compounds in published research follows the question being asked.
Eloralintide is used when researchers want to isolate amylin receptor pharmacology. With no GLP-1 activity, its effects on appetite, gastric emptying and body composition can be attributed to the amylin pathway. That also makes it the natural tool for add-on designs, where a GLP-1 or GLP-1/GIP agonist is already in place and the question is what amylin agonism adds. The EloraTZP programme and ENLIGHTEN-6 are both built on that logic.
Amycretin is used when the question is whether one molecule can match or exceed a two-drug combination. Its comparison point is CagriSema, which reported about 20.4% weight reduction at 68 weeks in REDEFINE 1 (PMID 40544433). Amycretin also gives researchers an oral peptide to study, which eloralintide does not currently offer.
Tolerability is a shared constraint. Both amylin-only and dual-agonist peptides produce dose-dependent nausea and vomiting, and dose titration schedules differ across trials. Researchers comparing designs can track registrations and readouts in the clinical trial tracker.
A third amylin analogue, petrelintide from Zealand Pharma and Roche, sits alongside eloralintide as a selective long-acting amylin agonist and is often included in the same comparisons.
Regulatory and compounding status
| Status | Eloralintide | Amycretin |
|---|---|---|
| FDA | Not approved; investigational | Not approved; investigational |
| EMA | Not approved | Not approved |
| 503A compounding | Not eligible | Not eligible |
| WADA | Prohibited under S0 (non-approved substances) | Prohibited under S0 (non-approved substances) |
Neither compound has a regulatory submission on file as of October 2026. Both are protected investigational molecules, so any material sold outside sanctioned trials is unverified.
Cited studies
- PMID 41207310, "Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial" (The Lancet, 2025). https://doi.org/10.1016/S0140-6736(25)02155-5
- PMID 42532080: "Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial" (The Lancet, 2026).
- PMID 42532079: "Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial" (The Lancet, 2026).
- PMID 40544433 · REDEFINE 1: cagrilintide-semaglutide in adults with overweight or obesity (NEJM, 2025). https://doi.org/10.1056/NEJMoa2502081
- Dahl K et al. "Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study" (The Lancet, 2025). https://doi.org/10.1016/S0140-6736(25)01185-7
Frequently asked questions
Q: What is the difference between eloralintide and amycretin?
A: Eloralintide activates the amylin receptor only, while amycretin activates both the amylin receptor and the GLP-1 receptor in a single molecule. Eloralintide is developed by Eli Lilly and amycretin by Novo Nordisk. Both are once-weekly injectable peptides in Phase 3 trials.
Q: Which showed more weight loss, eloralintide or amycretin?
A: Amycretin reported 22.0% to 24.3% mean weight reduction at 36 weeks in a 125-person Phase 1b/2a study, while eloralintide reported up to about 20% at 48 weeks in a 263-person Phase 2 trial. The trials differed in size, length and design, so the figures cannot be compared directly.
Q: Is amycretin the same as zenagamtide?
A: Yes. Zenagamtide is the name used for amycretin in later-stage development, including the 2026 Phase 2 type 2 diabetes trials published in The Lancet. Both names refer to the same unimolecular GLP-1 and amylin receptor agonist.
Q: Is eloralintide a GLP-1 agonist?
A: No. Eloralintide is a selective amylin receptor agonist with no GLP-1 receptor activity. This is why Lilly is studying it both alone and in combination with tirzepatide.
Q: Are eloralintide and amycretin FDA approved?
A: Neither compound is FDA approved as of October 2026. Both are investigational peptides in Phase 3 trials and are not eligible for 503A compounding. WADA prohibits both under its S0 category for non-approved substances.
See also:
- Eloralintide vs Cagrilintide: the selective amylin agonist compared with Novo's dual amylin/calcitonin agonist
- Amycretin vs Semaglutide: how the unimolecular co-agonist compares with GLP-1 monotherapy
- Cagrilintide and CagriSema: the two-molecule amylin plus GLP-1 approach amycretin aims to replace
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.