Peptide Research
Eloralintide (LY3841136): What Published Research Shows About Lilly’s Amylin Receptor Agonist
⚠ FOR EDUCATIONAL AND SCIENTIFIC REFERENCE PURPOSES ONLY. THIS ARTICLE SUMMARISES PUBLISHED CLINICAL LITERATURE AND IS NOT MEDICAL ADVICE. ELORALINTIDE IS AN INVESTIGATIONAL COMPOUND UNDER DEVELOPMENT BY ELI LILLY AND COMPANY AND IS NOT APPROVED FOR ANY USE IN ANY COUNTRY.
Quick answer: Eloralintide (LY3841136) is a long-acting, selective amylin receptor agonist being developed by Eli Lilly for obesity. In a 48-week Phase 2 trial published in The Lancet (November 2025), participants receiving eloralintide showed placebo-adjusted body-weight reductions of approximately 9.5% to 20%, with predominantly mild-to-moderate gastrointestinal adverse events. Phase 3 trials (the ENLIGHTEN programme) began in 2026 and are expected to run to 2028. Unlike GLP-1 receptor agonists, eloralintide acts on the amylin pathway, which is why it is being studied both alone and in combination with incretin-based therapies.
What Is Eloralintide?
Eloralintide is a synthetic peptide designed as a selective agonist of the amylin receptor. It is identified in the scientific literature by its development code LY3841136 and by CAS registry number 2883634-40-8. The compound and its use are described in Eli Lilly’s patent filings, including AU2022228541B2 and US 2022/0288168 A1 (“Long-acting amylin receptor agonists and uses thereof”).
Amylin is a 37-amino-acid hormone co-secreted with insulin by pancreatic beta cells. It acts on amylin receptors — heterodimers of the calcitonin receptor and receptor activity-modifying proteins (RAMPs) — located in areas of the brainstem and hypothalamus involved in satiety signalling. Native amylin has a short half-life and a tendency to aggregate, which historically limited its therapeutic development. Eloralintide was engineered for extended half-life and stability at neutral pH, allowing once-weekly administration in clinical trials.
Mechanism of Action
Published preclinical and clinical work describes eloralintide as acting primarily through three amylin-mediated pathways:
- Satiety signalling — activation of amylin receptors in the area postrema and related hindbrain regions, contributing to reduced food intake in animal and human studies.
- Delayed gastric emptying — a well-characterised effect of amylin agonism that prolongs post-meal fullness.
- Suppression of post-prandial glucagon — reducing hepatic glucose output after meals.
A distinguishing feature reported in the literature is eloralintide’s selectivity for the amylin receptor over the calcitonin receptor. Earlier dual amylin/calcitonin receptor agonists (DACRAs) showed efficacy but a different tolerability profile; selective agonism is hypothesised to retain weight-loss efficacy while reducing some of those effects. This remains an area of active investigation.
Phase 2 Trial Results (Lancet, 2025)
The Phase 2 study, published in The Lancet in November 2025 and presented at ObesityWeek 2025, enrolled adults with obesity or overweight without type 2 diabetes. Participants were randomised to one of several once-weekly eloralintide doses or placebo for 48 weeks.
Key findings reported by the investigators:
- Placebo-adjusted mean body-weight reduction ranged from approximately 9.5% at the lowest dose to 20.1% at the highest dose at 48 weeks, versus roughly 0.4% with placebo.
- Weight loss had not plateaued at 48 weeks in the higher-dose groups, suggesting further reduction may occur with longer treatment.
- Gastrointestinal adverse events (nausea, vomiting, diarrhoea) were the most common, but were reported as predominantly mild to moderate, with lower rates than typically reported in GLP-1 receptor agonist trials of similar efficacy.
- Discontinuation due to adverse events was low across dose groups.
A separate Phase 2 study evaluated eloralintide in combination with tirzepatide, exploring whether amylin and incretin pathways produce additive effects. Results from that combination arm have been reported as supporting further development.
How Eloralintide Differs From GLP-1 Receptor Agonists
| Feature | GLP-1 receptor agonists (e.g. semaglutide, tirzepatide) | Eloralintide (amylin receptor agonist) |
|---|---|---|
| Primary receptor | GLP-1 receptor (tirzepatide also GIP) | Amylin receptor (selective) |
| Main site of action | Pancreas, gut, hypothalamus | Area postrema / hindbrain, gut |
| Reported GI tolerability | Nausea common, dose-dependent | Lower nausea rates at comparable efficacy (Phase 2) |
| Regulatory status (2026) | Approved (multiple indications) | Investigational — Phase 3 ongoing |
| Development stage | Marketed | ENLIGHTEN Phase 3 programme, est. completion 2028 |
The other selective-amylin programme frequently discussed alongside eloralintide is Novo Nordisk’s cagrilintide, being developed in combination with semaglutide (CagriSema). Both programmes reflect broader industry interest in amylin agonism as a complement or alternative to incretin-based therapy — a theme also covered in our summary of weight regain after GLP-1 discontinuation.
Phase 3: The ENLIGHTEN Programme
Eli Lilly initiated Phase 3 trials of eloralintide in 2026 under the ENLIGHTEN programme. Registered studies include ENLIGHTEN-1 (adults with obesity or overweight) and ENLIGHTEN-2 (adults with obesity and type 2 diabetes), with primary completion dates currently listed in 2028. Additional trials are examining eloralintide in combination with tirzepatide and in weight-maintenance settings following initial weight loss.
Until these trials complete and are reviewed by regulators, eloralintide remains an investigational compound with no approved indication anywhere in the world.
Regulatory Status
Eloralintide is protected by active patents held by Eli Lilly and Company covering the compound, its sequence and its uses. It has not been approved by the FDA, EMA or any other regulatory authority. It is not available as a prescription medicine, and no compounded or generic version exists legally in any jurisdiction. For context on how the regulatory environment for research peptides is changing, see The Big Peptide Shift.
LiveWell Peptides publishes this summary as part of our research library. All compounds referenced on this site are for laboratory research use only.
Frequently Asked Questions
Is eloralintide the same as retatrutide?
No. Retatrutide is a triple agonist (GLP-1, GIP and glucagon receptors). Eloralintide is a selective amylin receptor agonist. They act on different pathways, though both are Eli Lilly investigational compounds for obesity.
How much weight loss was reported in trials?
In the 48-week Phase 2 study, placebo-adjusted weight reduction ranged from roughly 9.5% to 20.1% depending on dose, and had not plateaued at the study’s end.
Why is amylin agonism considered different from GLP-1?
Amylin acts mainly through hindbrain satiety centres and gastric emptying, while GLP-1 agonists act through incretin pathways. Phase 2 data suggested eloralintide achieved comparable weight loss with lower reported nausea, which is why combination approaches are being studied.
When could eloralintide be approved?
Phase 3 ENLIGHTEN trials are expected to complete around 2028. Any approval decision would follow regulatory review after that.
Is eloralintide available anywhere?
Not as a medicine. It is an investigational compound with no approved indication in any country, and no compounded or generic drug version exists. Research-grade eloralintide for in-vitro laboratory use is a separate category: LiveWell Peptides lists a 10 mg research vial (pre-order, research use only, not for human or animal use).
What remains unstudied?
Long-term durability beyond 48 weeks, weight maintenance after discontinuation, cardiovascular outcomes, and performance in people with type 2 diabetes are all still under investigation in the Phase 3 programme.
Download the white paper: The Peptide Blueprint, Special Issue: Eloralintide, The Weight Loss Peptide That Is Not a GLP-1 (PDF). A plain-English, 5 page summary of the Phase 1 and Phase 2 data, the amylin mechanism, and how it compares with cagrilintide, amycretin and the GLP-1 class, with 15 references.
Research-grade material: LiveWell Peptides now lists Eloralintide 10 mg research vial (coming soon, pre-orders open). For in-vitro laboratory research use only.
Related Research
Continue reading: GLP-1 Discontinuation and Weight Regain · Oral GLP-1 Receptor Agonists · The Big Peptide Shift
External context: PubMed · ClinicalTrials.gov
References
- Eloralintide Phase 2 trial in adults with obesity or overweight — The Lancet, November 2025.
- Eli Lilly and Company. Long-acting amylin receptor agonists and uses thereof. Patent AU2022228541B2; US 2022/0288168 A1.
- ClinicalTrials.gov. ENLIGHTEN-1 and ENLIGHTEN-2: Phase 3 studies of eloralintide (LY3841136).
- Hay DL et al. Amylin: pharmacology, physiology, and clinical potential. Pharmacological Reviews, 2015.
- Eloralintide (LY3841136), CAS 2883634-40-8. Chemical registry entry.
- Briere DA et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept. Mol Metab. 2025;102:102271. PMID 41109426
- Bhattachar S et al. Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept. Diabetes Obes Metab. 2026;28(4):2651-2660. PMID 41559929
- Kamrul-Hasan ABM et al. Novel amylin-based therapies for weight management in adults with overweight or obesity without diabetes: a network meta-analysis. Endocrinol Diabetes Metab. 2026;9(3):e70247. PMID 42175595
- Fischer SL, Borner T. Beyond GLP-1: Amylin-based pharmacotherapy and the search for better-tolerated weight-loss drugs. Pharmacol Res. 2026;232:108382. PMID 42586227
- Billings LK et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2 trial. Lancet. 2025;406(10520):2631-2643. PMID 41207310
⚠ FOR LABORATORY RESEARCH AND EDUCATIONAL PURPOSES ONLY — NOT FOR HUMAN OR ANIMAL CONSUMPTION. This article summarises publicly available scientific literature and does not constitute medical advice, an offer of sale, or a recommendation for use.