# Eloralintide

> Eloralintide is a long-acting synthetic lipidated peptide that acts as a selective agonist of the amylin receptor, with a preference for the amylin 1 receptor (AMY1R) over the calcitonin receptor. Developed under the code LY3841136, it has been studied in rats, monkeys, phase 1 trials and a 48-week phase 2 obesity trial. It is investigational and not FDA approved.

Canonical: https://peptideproperties.com/compounds/eloralintide/

## Identity

- **Class:** Incretin & Metabolic Receptor Agonists
- **Also known as:** LY3841136
- **Molecular formula:** C201H319N49O65S2
- **Molecular weight:** 4526 g/mol
- **Monoisotopic mass:** 4525.2671 Da
- **CAS number:** 2883634-40-8
- **PubChem CID:** 175663130
- **InChIKey:** RLBIFQNAUXZCQB-UHFFFAOYSA-N
- **Sequence notes:** Contains a methylene thioacetal (-S-CH2-S-) bridge between two cysteines, non-coded residues (alpha-methyl-phenylalanine, ornithine, N-methyl-asparagine), an N-terminal glutamic acid linked through its gamma-carboxyl, a lysine side chain acylated with a C20 diacid via two gamma-glutamic acid units, and a C-terminal tyrosine amide.

## Key facts

- Class: selective amylin receptor agonist (long-acting amylin analog)
- Receptor profile: preferentially activates human AMY1R over the calcitonin receptor and AMY3R in vitro
- Formula C201H319N49O65S2; molecular weight 4526 g/mol (PubChem CID 175663130)
- CAS Registry Number 2883634-40-8
- Development code LY3841136
- Clinical stage: phase 2 completed in adults with obesity or overweight
- Regulatory status: investigational; not FDA approved

## What Is Eloralintide?

Eloralintide is an investigational amylin analog designed as a selective agonist of the amylin receptor for research in obesity.[1][2] It was first reported under the development code LY3841136, and its published record spans in-vitro receptor assays, studies in rats and monkeys, and phase 1 and phase 2 clinical trials.[1][3][2]Amylin is a hormone co-secreted with insulin from pancreatic β-cells. It slows gastric emptying, suppresses glucagon secretion and promotes satiation through actions in the central nervous system.[4] The first approved amylin analog, pramlintide, established proof of concept but was limited by modest efficacy and a short duration of action, which prompted the design of long-acting successors.[5][6]Eloralintide belongs to this newer group of long-acting amylin-based agents, alongside cagrilintide, petrelintide and others in clinical development.[4][6] A 2026 review reports that these long-acting agents have shown clinically meaningful weight loss with generally favorable tolerability profiles.[6] It differs from cagrilintide mainly in receptor selectivity, a distinction reviewers consider potentially important for tolerability.[1][4]

## Chemical Structure and Molecular Identity

Eloralintide is a chemically modified, lipidated peptide. PubChem (CID 175663130) lists its molecular formula as C201H319N49O65S2 and its molecular weight as 4526 g/mol, and its CAS Registry Number is 2883634-40-8.
### Structural features

- Cyclic bridge: two cysteine residues are linked by a methylene thioacetal (–S–CH2–S–) bridge, forming a ring near the N-terminus.
- Non-coded residues: the PubChem structure includes α-methyl-phenylalanine, ornithine and N-methyl-asparagine.
- Lipidation: a lysine side chain carries an eicosanedioic (C20) fatty diacid attached through two gamma-glutamic acid units.
- Termini: an N-terminal glutamic acid linked through its side-chain carboxyl, and an amidated C-terminal tyrosine.Reviews attribute the long action of this generation of amylin analogs to peptide engineering, lipidation and reversible albumin binding.[4] Because of its non-coded residues and the thioacetal bridge, eloralintide's sequence cannot be written in the standard one-letter amino-acid code. The PubChem InChIKey is RLBIFQNAUXZCQB-UHFFFAOYSA-N.

## Research History and Development

Eloralintide moved from a combined discovery and first-in-human report in 2025 to a completed 48-week phase 2 trial published the same year, with a multiple-dose phase 1 study published in 2026.
### Discovery and single-dose phase 1
The discovery paper characterized eloralintide in cell lines expressing rat or human amylin 1 receptor (AMY1R), amylin 3 receptor (AMY3R) or calcitonin receptor (CTR), and in rats and monkeys.[1] The same report included a randomized, placebo-controlled single-ascending-dose study in 48 healthy participants with a mean BMI of 27.5 kg/m² (NCT05295940).[1]
### Multiple-dose phase 1
A 12-week, placebo-controlled multiple-ascending-dose study enrolled 100 participants with obesity or overweight at three US centers between 2022 and 2024. Participants had a mean age of 44 years and a mean BMI of 32.6 kg/m², and were assigned to five dose cohorts without dose escalation.[3]
### Phase 2
A 48-week, double-blind, placebo-controlled phase 2 trial enrolled 263 adults without type 2 diabetes at 46 US research centers (NCT06230523). It compared several fixed dose levels and two dose-escalation schemes with placebo, using percent change in body weight as the primary endpoint.[2] Participants had a mean body weight of 109.1 kg and mean BMI of 39.1 kg/m², and 78% were female; the study was completed in August 2025.[2] Efficacy analyses included all 263 randomized participants.[2]

## Mechanisms Studied in Research

Eloralintide is studied as an amylin receptor agonist that favors AMY1R, a receptor-selectivity profile its developers linked to lower food intake with less aversive signaling than a non-selective comparator in rats.[1]
### Receptor selectivity in vitro
In cell-based assays, eloralintide preferentially activated human AMY1R, with about 12-fold greater potency than at CTR and 11-fold greater than at AMY3R. At rat receptors, both AMY1R and AMY3R were activated more potently than CTR.[1]
### Animal models
In lean rats, eloralintide induced significantly less conditioned taste avoidance, a measure of aversive or malaise-like effects, than cagrilintide, which the authors described as a non-selective amylin receptor agonist.[1] In diet-induced obese rats, it reduced food intake and lowered body weight in a dose-dependent manner, primarily through loss of fat mass, and it showed favorable pharmacokinetics in rats and monkeys.[1]
### Why selectivity is studied
A 2026 review notes that long-acting amylin agents range from selective amylin receptor agonists to dual amylin/calcitonin receptor agonists. Calcitonin receptor engagement, exposure kinetics and hindbrain circuit recruitment may influence whether reduced food intake reflects physiological satiation or aversive signaling.[4]

## Key Findings From Published Studies

Published human studies report dose-related body-weight reductions with eloralintide compared with placebo, with gastrointestinal adverse events described as relatively infrequent in phase 1.[3][2]StudyPopulation and durationMain resultSingle-dose phase 1[1]48 healthy participants; week 4 after one doseBody weight −4.4% in the highest-dose cohort vs +0.6% with placeboMultiple-dose phase 1[3]100 adults with obesity or overweight; 12 weeksLeast squares mean weight reduction of 2.6% to 11.3% across dose groupsPhase 2[2][7]263 adults with obesity or overweight; 48 weeksWeight loss of 9% in the lowest-dose arm and up to 20.1% across arms
### Tolerability
In the single-dose study, 9 participants in the eloralintide cohorts reported 16 adverse events, 15 of them mild; two participants reported four gastrointestinal events, including one moderate vomiting event.[1] In the 12-week multiple-dose study, the most common treatment-emergent adverse events were decreased appetite (19%), headache (12%), fatigue (11%) and COVID-19 (11%), while diarrhea (10%), nausea (8%) and vomiting (4%) were less frequent. Exposure was dose proportional.[3]
### Cardiometabolic measures
A 2026 review of the early clinical studies reports reductions in pulse rate, blood pressure, high-sensitivity C-reactive protein and lipid parameters, along with preferential fat-mass loss. The authors note that the lower pulse rate contrasts with the heart-rate increase associated with GLP-1 receptor agonists.[8]
### Comparative analyses
A 2026 network meta-analysis of six trials (4,642 participants without diabetes) found that the highest-dose eloralintide stratum reduced body weight by 18.01% more than placebo, second only to high-dose subcutaneous amycretin. Gastrointestinal adverse events were more common with high-dose amylin-based therapies as a group, and the authors described the evidence as sparse and low-certainty.[9] Another 2026 review characterized eloralintide as an AMY1R-preferring monoagonist with a distinct adverse event profile.[7]Eloralintide's thioacetal bridge and non-coded residues make batch-specific HPLC and mass spectrometry certificates of analysis the practical way to confirm identity and purity.

## Regulatory and Research Status

Eloralintide is an investigational compound and is not approved by the US Food and Drug Administration (FDA). The published trials describe it as a selective amylin receptor agonist in development for weight management.[2][3]Recent reviews list eloralintide among the frontrunner amylin-based agents, together with the cagrilintide–semaglutide combination and zenagamtide, the name now used for amycretin.[7] Other reviews place it within a broader return of the amylin pathway to obesity research.[10][6] Across long-acting amylin analogs, nausea and other gastrointestinal effects are reported to be common during initiation and up-titration but mostly resolve with continued use.[5]Reviewers stress that current evidence comes from preclinical, phase 1 and phase 2 studies with relatively small samples and short durations, and that no amylin receptor agonist, including eloralintide, has been evaluated in a dedicated cardiovascular outcomes trial.[8] Outside registered clinical trials, eloralintide is not approved for human use, and material described as eloralintide is intended for laboratory research only.

## FAQ

**Is eloralintide FDA approved?**
No. Eloralintide is an investigational drug candidate. Its published phase 1 and phase 2 trials describe it as a selective amylin receptor agonist in development for weight management, and it has not received FDA approval. Outside registered clinical trials it is not approved for human use, and research material is intended for laboratory studies only.

**What is the molecular weight of eloralintide?**
PubChem (CID 175663130) lists eloralintide with a molecular weight of 4526 g/mol and the molecular formula C201H319N49O65S2. The structure is a lipidated peptide with a C20 fatty diacid, several non-coded amino acids and a methylene thioacetal bridge between two cysteines. Salt forms can show different mass values.

**How is eloralintide different from cagrilintide?**
Both are long-acting amylin analogs, but they differ in receptor selectivity. In cell assays eloralintide preferred the human amylin 1 receptor over the calcitonin receptor, while its discovery paper describes cagrilintide as non-selective. In lean rats, eloralintide caused significantly less conditioned taste avoidance than cagrilintide.

**What is LY3841136?**
LY3841136 is the development code for eloralintide. The code appears in the 2025 discovery and clinical proof-of-concept paper in Molecular Metabolism, which covered receptor assays, rat and monkey studies and a single-dose phase 1 trial, and in the 2026 multiple-ascending-dose phase 1 study.

**Is eloralintide a GLP-1 agonist?**
No. Eloralintide is an amylin receptor agonist, not a GLP-1 receptor agonist. It acts on amylin receptors, which are complexes of the calcitonin receptor with accessory proteins, and preferentially activates the AMY1R subtype. A 2026 review notes that its reduction in pulse rate contrasts with the heart-rate increase seen with GLP-1 receptor agonists.

**What does the research on eloralintide show?**
In a 48-week phase 2 trial in 263 adults with obesity or overweight, weight loss ranged from 9% in the lowest-dose arm to as much as 20.1%. In a 12-week phase 1 study, weight fell by 2.6% to 11.3% across dose groups, with relatively few gastrointestinal events. No cardiovascular outcomes trial has been reported.

## References

1. Briere DA, Qu H, Lansu K, et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept. Molecular metabolism 2025. PMID: 41109426
2. Billings LK, Hsia S, Bays H, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet (London, England) 2025. PMID: 41207310
3. Bhattachar S, Tham LS, Tidemann-Miller B, et al. Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept. Diabetes, obesity & metabolism 2026. PMID: 41559929
4. Fischer SL, Borner T. Beyond GLP-1: Amylin-based pharmacotherapy and the search for better-tolerated weight-loss drugs. Pharmacological research 2026. PMID: 42586227
5. Bailey CJ, Flatt PR, Conlon JM. Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. Peptides 2026. PMID: 41747885
6. Alhazmi A, le Roux CW. Amylin Analogs: The Next Major Class of Weight Loss Therapy: A Review of Experimental Data and Early-Phase Clinical Trials. Diabetes, obesity & metabolism 2026. PMID: 42452898
7. Panou T, Gouveri E, Popovic DS, et al. New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus. Diabetes therapy : research, treatment and education of diabetes and related disorders 2026. PMID: 42803913
8. Sigalov A, Frishman WH. Cardiometabolic Risk Reduction Through Selective Amylin Receptor Agonism: Emerging Cardiovascular Implications of Eloralintide. Cardiology in review 2026. PMID: 42745233
9. Kamrul-Hasan ABM, Khalil I, Mahajan K, et al. Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis. Endocrinology, diabetes & metabolism 2026. PMID: 42175595
10. Lempesis IG, Dalamaga M. Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies. Metabolism open 2026. PMID: 41948476