# Eloralintide — Research Peptide Profile

> Eloralintide (LY3841136) is Lilly's AMY1R-selective amylin agonist. Phase 2: 9-20% weight loss at 48 weeks vs 0.4% placebo, once weekly. Trial data & safety.

Source: https://peptpedia.org/peptide/eloralintide | Published: 2026-09-18 | Last updated: 2026-09-18

Eloralintide (LY3841136) is Eli Lilly's once-weekly amylin analog engineered to preferentially activate the AMY1R amylin receptor. In a 48-week Phase 2 trial in 263 adults with obesity, it produced dose-dependent mean weight loss of 9% to 20% versus 0.4% with placebo, with nausea and fatigue the most common adverse events. It is investigational, with Phase 3 trials now recruiting.

## Overview

Eloralintide (LY3841136) is a synthetic, once-weekly amylin analog developed by Eli Lilly for the treatment of obesity. It is a C-terminally amidated linear polypeptide of 37 amino acids built on the human amylin scaffold, containing three non-coded residues (positions 11, 15, and 22), a methylene thioacetal bridge replacing the native disulfide, and a C20 fatty diacid side chain at Lys26 that binds albumin to extend its half-life. Its defining pharmacological feature is receptor selectivity: it activates the human AMY1R amylin receptor 12-fold more potently than the calcitonin receptor (CTR) and 11-fold more potently than AMY3R, whereas the older amylin analog [cagrilintide](/peptide/cagrilintide) is non-selective. In a 48-week Phase 2 trial in 263 adults with obesity or overweight, once-weekly eloralintide produced dose-dependent mean weight loss of 9% to 20% versus 0.4% with placebo. Lilly has also completed a Phase 1 combination study with [tirzepatide](/peptide/tirzepatide) (NCT06916065), and Phase 3 monotherapy trials are recruiting as of 2026. It remains investigational and unapproved.

## Molecular Profile

- **Category:** metabolic
- **Molecular formula:** C201H319N49O65S2
- **Molecular weight:** 4526 g/mol
- **CAS number:** 2883634-40-8
- **Amino acid sequence:** Lipidated 37-amino-acid human amylin analog; Cys2-Cys7 methylene thioacetal bridge, 3 non-coded residues (positions 11, 15, 22), C20 fatty diacid at Lys26, C-terminally amidated
- **Also known as:** LY3841136, LY-3841136
- **Half-life:** 310-366 hours (12.9-15.3 days) terminal half-life across 0.4-12 mg single doses (PMID 41109426)

## Mechanism of Action

Amylin is a 37-amino-acid peptide hormone co-secreted with insulin from pancreatic beta cells in response to nutrient intake; it suppresses prandial glucagon, slows gastric emptying, and promotes satiety through amylin receptors in hindbrain regions including the area postrema. Amylin receptors are heterodimers of the calcitonin receptor with receptor activity-modifying proteins (RAMP1-3), and AMY1R is the calcitonin receptor-RAMP1 complex. Eloralintide was engineered to preferentially activate AMY1R over the calcitonin receptor and AMY3R, a profile intended to retain amylin-pathway satiety signaling while reducing the gastrointestinal effects associated with non-selective receptor activation. In lean rats it produced significantly less conditioned taste avoidance, a preclinical proxy for nausea, than the non-selective agonist cagrilintide (p < 0.05). The C20 fatty diacid side chain at Lys26 binds serum albumin, extending the terminal half-life to 310-366 hours (12.9-15.3 days) in humans and supporting once-weekly subcutaneous dosing.

## Key Research Findings

- In a 48-week Phase 2 trial (263 participants), once-weekly eloralintide produced dose-dependent mean weight loss of 9-20% versus 0.4% with placebo, with trajectories not yet plateaued at trial end.
- Eloralintide activates human AMY1R 12-fold more potently than the calcitonin receptor and 11-fold more potently than AMY3R, a selectivity engineered to improve gastrointestinal tolerability.
- Terminal half-life of 310-366 hours (12.9-15.3 days) supports once-weekly subcutaneous dosing with low peak-to-trough variation.
- In obese rats, fat mass accounted for the majority of eloralintide-induced weight loss, with significantly less lean mass loss than cagrilintide in head-to-head preclinical comparison (p = 0.0101).

## Once-Weekly Pharmacology: Albumin Binding and a 13-15 Day Half-Life

Eloralintide's pharmacokinetics have been characterized in rats, cynomolgus monkeys, and two Phase 1 human studies published with its discovery paper and in a dedicated multiple-ascending-dose trial.

### Absorption and Elimination

Single-ascending-dose data from 48 healthy participants define the human exposure profile.

- Median time to maximum concentration was 72-132 hours across the 0.04-12 mg single-dose range, reflecting slow subcutaneous absorption (PMID 41109426).
- Terminal geometric mean half-life was 310-366 hours (12.9-15.3 days) across the 0.4-12 mg range, and exposure was dose proportional between 0.4 and 12 mg (PMID 41109426).
- For class context, cagrilintide's half-life is 159-195 hours (6.6-8.1 days); eloralintide's longer half-life produces lower peak-to-trough variation at weekly dosing (PMID 41109426).

### Structural Basis of Half-Life Extension

Two chemical modifications distinguish eloralintide from native amylin.

- A saturated linear C20 fatty diacid attached to Lys26 through a two-glutamate linker binds serum albumin, slowing clearance in the same fashion as acylated incretin peptides (PMID 41109426).
- The native amylin disulfide bridge is replaced by a methylene thioacetal bridge, improving chemical stability and resistance to fibril formation (PMID 41109426).
- Three non-coded amino acid residues at positions 11, 15, and 22 confer receptor selectivity and developability properties (PMID 41109426).

### Multiple-Dose Behavior

The 12-week multiple-ascending-dose study tested weekly dosing without escalation in 100 participants with obesity or overweight.

- Steady-state exposure was dose proportional, and mean body weight reductions at week 12 ranged from 2.6% to 11.3% across dose groups (PMID 41559929).
- Gastrointestinal adverse events were infrequent (diarrhea 10%, nausea 8%, vomiting 4%), and most treatment-emergent events were mild (PMID 41559929).
- The most common treatment-emergent events were decreased appetite (19%), headache (12%), and fatigue (11%); one serious adverse event occurred and was judged unrelated to eloralintide (PMID 41559929).

## Safety & Tolerability

Eloralintide's adverse event profile is dominated by dose-related gastrointestinal effects, principally nausea, and fatigue, both attenuated by slower dose escalation. In Phase 1 studies most events were mild and gastrointestinal events were infrequent. Human exposure is limited to Lilly-sponsored Phase 1 and Phase 2 trials totaling a few hundred participants and at most 48 weeks of dosing.

**Human data status:** Published human data consists of two Phase 1 studies (single ascending doses in 48 healthy participants; 12-week multiple ascending doses in 100 participants with obesity or overweight) and one 48-week Phase 2 trial in 263 participants. Phase 3 trials are recruiting as of 2026; no post-marketing or long-term data exists.

**Regulatory status:** Investigational; not approved by the FDA or any other regulatory agency. Available only within Eli Lilly-sponsored clinical trials. No licensed research-use formulation exists.

- In the 48-week Phase 2 trial, the most common adverse events were nausea (11-64% across arms, highest in the fixed 6 mg arm) and fatigue (up to 46% in the 6-9 mg escalation arm); placebo rates were 14% and 12% respectively, and both effects were dose-related and reduced with slower escalation. (evidence tier: human-interventional; [PMID 41207310](https://pubmed.ncbi.nlm.nih.gov/41207310/))
- In the single-ascending-dose Phase 1 study, 9 of 36 eloralintide-treated participants reported 16 adverse events, 15 of them mild; gastrointestinal events occurred in only 2 participants, and no clinically meaningful changes in vitals, ECG, or laboratory parameters were reported. (evidence tier: human-interventional; [PMID 41109426](https://pubmed.ncbi.nlm.nih.gov/41109426/))
- In the 12-week multiple-ascending-dose study, gastrointestinal events were infrequent (diarrhea 10%, nausea 8%, vomiting 4%), most treatment-emergent events were mild, and the single serious adverse event was judged unrelated to eloralintide. (evidence tier: human-interventional; [PMID 41559929](https://pubmed.ncbi.nlm.nih.gov/41559929/))
- No data exist beyond 48 weeks of continuous treatment; effects of discontinuation, weight regain trajectory, and safety in pregnancy, lactation, and pediatric populations are uncharacterized. (evidence tier: theoretical; [PMID 41747885](https://pubmed.ncbi.nlm.nih.gov/41747885/))

## Dosing Information (Research Context)

In the published Phase 2 trial, eloralintide was administered once weekly by subcutaneous injection at doses of 1, 3, 6, and 9 mg, with additional arms escalating from 6 mg or 3 mg to 9 mg, for 48 weeks (PMID 41207310). Phase 1 studies evaluated single doses of 0.04-12 mg in healthy participants and once-weekly multiple doses for 12 weeks in participants with obesity or overweight (PMIDs 41109426, 41559929). No dosing outside Eli Lilly-sponsored trials has been published.

| Route | Dose | Frequency | Notes |
| --- | --- | --- | --- |
| Subcutaneous (Phase 2) | 1, 3, 6, or 9 mg | Once weekly x 48 weeks | Fixed doses or 3-9 mg / 6-9 mg escalation; NCT06230523, 263 participants |
| Subcutaneous (Phase 1 single dose) | 0.04-12 mg | Single dose | NCT05295940; -2.5% (4 mg) and -4.4% (12 mg) body weight at day 29 |
| Subcutaneous (Phase 1 multiple dose) | Multiple ascending cohorts | Once weekly x 12 weeks | No dose escalation; 2.6-11.3% weight reduction; PMID 41559929 |

## Researched Effects

- **Weight Reduction** (evidence: moderate): Eloralintide produced clinically meaningful, dose-dependent weight loss across its published trial program. In the 48-week Phase 2 trial (263 participants at 46 US centers), mean percent body weight change was -9% at 1 mg, -12% at 3 mg, -18% at 6 mg, and -20% in both the 9 mg and 6-9 mg escalation arms, versus -0.4% with placebo. Weight loss trajectories had not plateaued at week 48, suggesting longer treatment may yield further reduction. Phase 1 data showed the effect begins early: single 4 mg and 12 mg doses produced -2.5% and -4.4% body weight at day 29 versus +0.6% with placebo, and 12 weeks of once-weekly dosing produced 2.6-11.3% reductions across dose groups. The magnitude of effect at the top doses approaches the range reported for dual incretin agonists, achieved through the amylin pathway alone.
- **Gastrointestinal Tolerability Profile** (evidence: preliminary): Eloralintide was designed to improve the gastrointestinal tolerability of amylin therapy through AMY1R selectivity, on the rationale that calcitonin receptor activation contributes to nausea. In lean rats it produced significantly less conditioned taste avoidance, a preclinical proxy for emesis, than the non-selective agonist cagrilintide. Human data is directionally consistent: only 2 of 36 eloralintide-treated participants in the single-ascending-dose study reported any gastrointestinal event, and nausea occurred in just 8% of participants in the 12-week multiple-dose study. In the 48-week Phase 2 trial, nausea remained the most common adverse event (11-64% across arms versus 14% with placebo) but was substantially lower in arms using slower dose escalation. No head-to-head human trial against cagrilintide exists, so the comparative tolerability advantage remains an unproven mechanistic hypothesis.
- **Fat-Predominant Weight Loss** (evidence: preliminary): In diet-induced obese rats, eloralintide reduced body weight primarily through fat mass loss, with fat accounting for approximately 68-85% of total weight loss across tested doses. In a direct preclinical comparison, repeated eloralintide dosing produced comparable fat loss to cagrilintide but significantly less lean mass loss (p = 0.0101), with fat accounting for 80-91% of weight loss versus 63% for cagrilintide. Lean mass preservation during pharmacological weight reduction is a central concern with incretin-class therapies, making this signal pharmacologically important. Body composition data from the human trials has not been published, so the finding remains preclinical.

## Research Applications

- Obesity Pharmacotherapy Research
- Amylin Receptor Biology
- Weight Management Clinical Trials
- Body Composition Research

## Key Studies

### Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept

Briere DA, Qu H, Lansu K, et al. — *Molecular Metabolism* (2025) — [PMID 41109426](https://pubmed.ncbi.nlm.nih.gov/41109426/) | [doi:10.1016/j.molmet.2025.102271](https://doi.org/10.1016/j.molmet.2025.102271)

This discovery paper from Eli Lilly characterized eloralintide from bench to first-in-human dosing. In vitro, eloralintide preferentially activated human AMY1R (12-fold over CTR, 11-fold over AMY3R) with full agonism, and the paper details its structure: a 37-amino-acid amidated amylin analog with three non-coded residues, a methylene thioacetal bridge, and a C20 fatty diacid at Lys26. In diet-induced obese rats it reduced food intake and body weight primarily through fat loss, and it induced significantly less conditioned taste avoidance than cagrilintide. The embedded Phase 1 single-ascending-dose trial (48 healthy participants, 0.04-12 mg) found a half-life of 310-366 hours supporting once-weekly dosing, mostly mild adverse events, and -2.5% (4 mg) and -4.4% (12 mg) body weight change at day 29 versus +0.6% with placebo.

### Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial

Billings LK, Hsia S, Bays H, et al. — *The Lancet* (2025) — [PMID 41207310](https://pubmed.ncbi.nlm.nih.gov/41207310/) | [doi:10.1016/S0140-6736(25)02155-5](https://doi.org/10.1016/S0140-6736(25)02155-5)

This Phase 2 trial enrolled 263 adults (mean BMI 39.1) with obesity or overweight plus at least one weight-related comorbidity, without type 2 diabetes, across 46 US centers, randomizing them to once-weekly eloralintide (1, 3, 6, or 9 mg, or 6-9 mg or 3-9 mg escalations) or placebo for 48 weeks. Mean percent body weight change was -9% (1 mg), -12% (3 mg), -18% (6 mg), -20% (9 mg), -20% (6-9 mg), and -16% (3-9 mg) versus -0.4% with placebo, and all eloralintide arms met the primary endpoint. The most common adverse events were nausea (11-64% across arms versus 14% placebo) and fatigue (up to 46% versus 12% placebo), both dose-related and attenuated by slower escalation. Weight loss trajectories had not plateaued at week 48.

### Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept

Bhattachar S, Tham LS, Tidemann-Miller B, et al. — *Diabetes, Obesity and Metabolism* (2026) — [PMID 41559929](https://pubmed.ncbi.nlm.nih.gov/41559929/) | [doi:10.1111/dom.70439](https://doi.org/10.1111/dom.70439)

This 12-week Phase 1 multiple-ascending-dose study randomized 100 participants with obesity or overweight to once-weekly eloralintide or placebo across five cohorts without dose escalation. Steady-state exposure was dose proportional. The most common treatment-emergent adverse events were decreased appetite (19%), headache (12%), fatigue (11%), and COVID-19 (11%); gastrointestinal events were infrequent (diarrhea 10%, nausea 8%, vomiting 4%) and mostly mild. Least-squares mean body weight reduction at week 12 ranged from 2.6% to 11.3% across dose groups, establishing multiple-dose proof of concept for once-weekly administration.

### Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes

Bailey CJ, Flatt PR, Conlon JM — *Peptides* (2026) — [PMID 41747885](https://pubmed.ncbi.nlm.nih.gov/41747885/) | [doi:10.1016/j.peptides.2026.171480](https://doi.org/10.1016/j.peptides.2026.171480)

This independent review places eloralintide within the second generation of long-acting amylin analogs that followed pramlintide, the first therapeutically useful amylin agonist, which was limited by a short half-life requiring 2-3 daily doses. The authors explain how understanding of amylin-calcitonin receptor heterodimer structure enabled non-aggregating, long-acting designs, and list eloralintide among recently developed analogs (with petrelintide, MET-233, and AZD6234) showing strong monotherapy efficacy in clinical trials. The review also covers cagrilintide and its co-formulation with semaglutide (CagriSema), and notes gastrointestinal side effects, especially nausea, as the class-wide tolerability challenge that selective designs aim to address.

## Frequently Asked Questions

### How much weight loss did eloralintide produce in clinical trials?

In the 48-week Phase 2 trial in 263 adults with obesity or overweight, once-weekly eloralintide produced mean body weight reductions of 9% (1 mg), 12% (3 mg), 18% (6 mg), and 20% (9 mg and the 6-9 mg escalation) versus 0.4% with placebo (PMID 41207310). Weight loss curves had not plateaued at week 48. Phase 1 studies showed the effect starts early: single 4 mg and 12 mg doses reduced body weight 2.5% and 4.4% at day 29, and 12 weeks of weekly dosing produced 2.6-11.3% reductions (PMIDs 41109426, 41559929).

### How is eloralintide different from cagrilintide?

Both are once-weekly amylin analogs, but they differ in receptor selectivity. Cagrilintide non-selectively activates amylin receptors and the calcitonin receptor (CTR). Eloralintide activates human AMY1R 12-fold more potently than CTR and 11-fold more potently than AMY3R. The design rationale is that CTR activation may contribute to gastrointestinal side effects; in lean rats, eloralintide caused significantly less conditioned taste avoidance than cagrilintide. No head-to-head human trial exists, so the tolerability advantage is supported only by indirect comparison, not direct evidence.

### What are the side effects of eloralintide?

In the 48-week Phase 2 trial, the most common adverse events were nausea (11-64% across dose arms versus 14% with placebo) and fatigue (up to 46% versus 12% with placebo). Both were dose-related and were substantially reduced with slower dose escalation. In Phase 1 studies, most adverse events were mild and gastrointestinal events were infrequent (nausea 8%, vomiting 4% in the 12-week study). Safety beyond 48 weeks of treatment has not been characterized, and use in pregnancy or pediatric populations has not been studied.

### Is eloralintide FDA approved?

No. Eloralintide is investigational and not approved by the FDA or any other regulator. Its published evidence consists of Phase 1 studies and one 48-week Phase 2 trial; Phase 3 trials in obesity (with and without type 2 diabetes) are recruiting as of 2026. It is available only within Eli Lilly-sponsored clinical trials, and material sold by gray-market vendors has no verified identity or purity.

### How does eloralintide work?

Eloralintide mimics the hormone amylin, which is co-secreted with insulin after meals and promotes satiety through receptors in the hindbrain. It preferentially activates the AMY1R receptor, a heterodimer of the calcitonin receptor and RAMP1, reducing food intake. A C20 fatty diacid side chain binds albumin in the bloodstream, giving it a 310-366 hour (roughly 13-15 day) half-life that supports once-weekly injection.

## Related Peptides

- [Cagrilintide](https://peptpedia.org/peptide/cagrilintide)
- [Pramlintide](https://peptpedia.org/peptide/pramlintide)
- [Tirzepatide (GLP-1/GIP)](https://peptpedia.org/peptide/tirzepatide)
- [CagriSema](https://peptpedia.org/peptide/cagrisema)

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