Peptide Research
Eloralintide (LY3841136): Selective Amylin Receptor Agonist — Mechanism and Published Evidence
Key Takeaways
- Eloralintide (LY3841136) is an investigational selective amylin receptor agonist that preferentially activates the amylin 1 receptor (AMY1R) over the calcitonin receptor and AMY3R in human in vitro assays, distinguishing it from dual agonists like cagrilintide.
- Preclinical studies suggest eloralintide may induce less aversive signaling, such as conditioned taste avoidance, compared to cagrilintide, potentially due to its receptor selectivity.
- Phase 1 and Phase 2 clinical trials have reported dose-dependent reductions in body weight among participants, with gastrointestinal events such as nausea and diarrhea occurring at varying frequencies.
- A network meta-analysis of randomized trials ranks high-dose eloralintide favorably in terms of body-weight change compared to other amylin analogues, although the evidence is described as sparse and low-certainty.
- Eloralintide remains an investigational compound not approved for clinical use, with research-grade material intended solely for laboratory research applications.
Eloralintide (development code LY3841136) is a selective amylin receptor agonist developed by Eli Lilly and studied as an investigational treatment for obesity. It preferentially activates the amylin 1 receptor (AMY1R) — 12-fold over the calcitonin receptor and 11-fold over AMY3R in human in vitro assays — which distinguishes it from dual amylin/calcitonin agonists such as cagrilintide. Published pharmacokinetics support once-weekly subcutaneous dosing.
Scope. This article reviews published literature. All clinical figures come from trials of Eli Lilly’s investigational drug product in enrolled human participants. Research-grade material is not that clinical formulation and is for laboratory research use only — not for human or veterinary use. No human dosing guidance is given or implied.
Mechanism of action
Eloralintide agonises the amylin 1 receptor, a heterodimer of the calcitonin receptor with receptor activity-modifying protein 1 (RAMP1). Amylin is a pancreatic beta-cell hormone co-secreted with insulin that slows gastric emptying, suppresses glucagon secretion and promotes satiation via hindbrain and parabrachial circuits.
Why receptor selectivity is the point
The hypothesis in the literature is that calcitonin receptor engagement contributes to aversive signalling — nausea and malaise — rather than to satiation. Preclinically, eloralintide induced significantly less conditioned taste avoidance in lean rats than cagrilintide (p < 0.05).
Published clinical evidence
Phase 1 single ascending dose (NCT05295940). 48 healthy participants, 0.04–12 mg single dose. Week-4 body weight change was −2.5% at 4 mg and −4.4% at 12 mg, against +0.6% for placebo.
Phase 1 multiple ascending dose. 100 participants over 12 weeks of once-weekly dosing. Week-12 weight reduction ranged 2.6%–11.3% across dose groups. Gastrointestinal events were infrequent: diarrhoea 10%, nausea 8%, vomiting 4%.
Phase 2 (NCT06230523). 263 participants across 46 US centres, 48 weeks. Mean change in body weight from baseline was −9% at 1 mg, −12% at 3 mg, −18% at 6 mg and −20% at 9 mg, against −0.4% for placebo. Nausea ranged 11%–64% across dose arms and fatigue 0%–46%.
How it compares with other amylin analogues
A network meta-analysis of six randomised trials (N = 4,642) ranked high-dose eloralintide second at −18.01% percent body-weight change versus placebo (P score 0.89), behind high-dose amycretin (−23.95%) and ahead of CagriSema (−17.18%), semaglutide 2.4 mg (−11.45%) and liraglutide 3.0 mg (−6.4%). The authors describe the evidence base as sparse and low-certainty.
Frequently asked questions
What is eloralintide? Eloralintide, development code LY3841136, is a selective amylin receptor agonist developed by Eli Lilly and studied as an investigational treatment for obesity. It is a long-acting amylin analogue given once weekly by subcutaneous injection in published trials. It is not an approved medicine.
How is eloralintide different from cagrilintide? Receptor selectivity. Cagrilintide is a dual amylin/calcitonin receptor agonist; eloralintide preferentially activates AMY1R — 12-fold over the calcitonin receptor and 11-fold over AMY3R in human in vitro assays.
What is the mechanism of action of eloralintide? It agonises the amylin 1 receptor, a heterodimer of the calcitonin receptor with RAMP1, acting through central satiation circuits.
Is eloralintide not FDA-approved? No. It is an investigational compound in clinical development. Research-grade eloralintide is sold for laboratory research use only.
How should research-grade eloralintide be stored? Lyophilised peptide is typically stored at −20°C, protected from light and moisture. After reconstitution, refrigerated storage and minimal freeze-thaw cycling are standard practice. Follow the handling guidance on the certificate of analysis for the specific lot.
References
Bibliographic records retrieved from PubMed.
1. Briere DA, et al. Molecular Metabolism. 2025;102:102271. https://doi.org/10.1016/j.molmet.2025.102271
2. Billings LK, et al. The Lancet. 2025;406(10520):2631-2643. https://doi.org/10.1016/S0140-6736(25)02155-5
3. Bhattachar S, et al. Diabetes, Obesity & Metabolism. 2026;28(4):2651-2660. https://doi.org/10.1111/dom.70439
4. Kamrul-Hasan ABM, et al. Endocrinology, Diabetes & Metabolism. 2026;9(3):e70247. https://doi.org/10.1002/edm2.70247
5. Fischer SL, Borner T. Pharmacological Research. 2026;232:108382. https://doi.org/10.1016/j.phrs.2026.108382
6. Bailey CJ, et al. Peptides. 2026;196:171480. https://doi.org/10.1016/j.peptides.2026.171480
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