Eloralintide Research Overview (also known as Obesity & Weight Management)
Eloralintide (LY3841136) is a novel once-weekly, selective AMY1R amylin receptor agonist developed by Eli Lilly for the treatment of obesity. Unlike cagrilintide, which non-selectively activates amylin and calcitonin receptors, eloralintide demonstrates 11- to 12-fold selectivity for the human AMY1R receptor over CTR and AMY3R, a design choice believed to drive its markedly improved gastrointestinal tolerability while preserving robust weight-loss efficacy. In a 48-week Phase 2 trial (NCT0623052
What Is Eloralintide?
Eloralintide (LY3841136) is a novel once-weekly, selective AMY1R amylin receptor agonist developed by Eli Lilly for the treatment of obesity. Unlike cagrilintide, which non-selectively activates amylin and calcitonin receptors, eloralintide demonstrates 11- to 12-fold selectivity for the human AMY1R receptor over CTR and AMY3R, a design choice believed to drive its markedly improved gastrointestinal tolerability while preserving robust weight-loss efficacy. In a 48-week Phase 2 trial (NCT06230523) in 263 adults with obesity, monotherapy produced dose-dependent mean body weight reductions of 9.5% to 20.1% versus 0.4% with placebo, with weight loss curves not yet plateauing at week 48. Eli Lilly announced plans to initiate Phase 3 monotherapy trials by year-end 2025, and is concurrently evaluating eloralintide in combination with tirzepatide in the ATTAIN Phase 2 program.
Mechanism of Action
Subcutaneous injection allows the lipidated, albumin-binding peptide to achieve sustained plasma exposure. Eloralintide selectively activates AMY1R in the brainstem area postrema and hypothalamus, driving satiety and reduced food intake while sparing CTR-mediated GI side effects.
Key Benefits
Once-weekly subcutaneous dosing supported by 13–15 day half-life. Up to 20.1% mean body weight loss at 48 weeks in Phase 2 with markedly improved GI tolerability versus non-selective amylin agonists. Potential combination partner for tirzepatide.
Quick Reference
| Literature-Reported Dose Range | 1–9 mg weekly (under Phase 2 evaluation) |
| Literature-Reported Frequency | Once weekly (supported by 13–15 day half-life) |
| Literature-Reported Cycle Length | Continuous |
| Literature-Reported Washout | Not established; long-term durability data not yet available |
| Storage | Refrigerated 2–8°C |
| Sites Reported in Studies | SubQ — abdomen, thigh, or upper arm (rotate weekly) |
| Timing | Same day each week, with or without food |
Research Indications
Weight Loss
Phase 2 Monotherapy Efficacy
Dose-dependent mean body weight reductions of 9.5% (1 mg) to 20.1% (9 mg) at 48 weeks (NCT06230523, N=263).
Curve Not Yet Plateauing
Weight loss continued to progress through week 48, suggesting longer Phase 3 trials may show further reduction.
Body Composition Quality
Preclinical data show 85% of weight loss is attributable to fat mass with significantly less lean mass loss than cagrilintide.
Appetite Control
AMY1R-Selective Satiety
Selective activation of the AMY1R hindbrain pathway reduces food intake without engaging CTR-mediated nausea pathways as strongly as non-selective agonists.
Lower Conditioned Taste Avoidance
Preclinical models show eloralintide induces significantly less conditioned taste aversion than cagrilintide (p<0.05).
Slower Gastric Emptying
Class-typical delay in gastric emptying contributes to increased satiety and reduced caloric intake.
Cardiovascular
Improved Lipid Profile
Phase 2 trial reported improvements in lipid profile across treatment arms.
Reduced Inflammatory Burden
hsCRP concentrations decreased over 48 weeks, signaling improved cardiometabolic risk.
Blood Pressure Reduction
Treatment was associated with reductions in blood pressure consistent with weight loss magnitude.
Metabolic
Glycemic Improvement
Improvements in glycemic markers reported in Phase 2; ATTAIN trial (NCT06603571) is testing efficacy in adults with T2D.
Waist Circumference Reduction
Waist circumference improved across treatment arms.
Cardiometabolic Risk Reduction
Composite improvements in lipids, BP, glucose, and inflammation suggest broad cardiometabolic benefit.
Research Protocols
As reported in cited literature and research-community logs (see Research Citations below) — not a personal dosing recommendation.
| Research Application | Dose | Frequency | Route |
|---|
| Phase 2 Low Dose (Monotherapy) | 1 mg weekly | Once weekly | SubQ |
| Phase 2 Mid Dose | 3 mg weekly | Once weekly | SubQ |
| Phase 2 High Dose | 6 mg weekly | Once weekly | SubQ |
| Phase 2 Maximum Dose | 9 mg weekly | Once weekly | SubQ |
| Slow Dose Escalation | 3 mg → 9 mg over multiple weeks | Once weekly with stepwise escalation | SubQ |
| Combination with Tirzepatide (ATTAIN — Investigational) | Eloralintide + tirzepatide (doses under study) | Once weekly each | SubQ (separate injections) |
Timing
Recommended administration window: same day each week, with or without food. Typical onset: onset: appetite suppression within first weeks; meaningful weight loss by 4–12 weeks; trajectory continuing through 48 weeks.
Peptide Interactions
Active investigation in the ATTAIN Phase 2 program (NCT06603571) evaluating eloralintide combined with tirzepatide. Complementary mechanisms — AMY1R-selective amylin agonism plus dual GIP/GLP-1 receptor activation — are hypothesized to drive additive weight loss while leveraging eloralintide's superior GI tolerability profile.
Both compounds are amylin receptor agonists. Cagrilintide is non-selective (activates AMY1R, AMY3R, and CTR with comparable potency), while eloralintide is AMY1R-selective. Combining them would provide no additive benefit, would compound GI risk, and would defeat the tolerability rationale behind eloralintide's selective design.
Pramlintide is a short-acting amylin analog requiring 2–3 daily doses. Overlapping mechanism with eloralintide provides no incremental benefit and increases risk of cumulative GI side effects and excessive gastric-emptying delay.
No published direct combination trial with eloralintide. The closely-related cagrilintide + semaglutide combination (CagriSema) is well characterized, suggesting eloralintide + semaglutide would be pharmacologically reasonable but is not currently part of Lilly's published development program. Monitor for additive GI effects if attempted off-label.
Both produce significant GI effects, although eloralintide's AMY1R-selective design reduces GI burden relative to non-selective amylin agonists. Retatrutide's triple agonism is associated with substantial nausea/vomiting at higher doses. No combination data exists; concomitant use is not supported by clinical evidence.
Amylin agonists slow gastric emptying and reduce postprandial glucose excursions. Patients on insulin therapy may require dose reduction or timing adjustment to avoid hypoglycemia, particularly during dose escalation. Closely monitor blood glucose.
No known pharmacokinetic interactions. Both target distinct pathways (AMP-kinase activation vs. amylin receptor signaling). Combination is expected to be well tolerated based on the broader class precedent for amylin analogs with metformin.
Different mechanisms (renal glucose excretion vs. central satiety and gastric emptying). No known interactions expected; combination is consistent with broader cardiometabolic management standards.
Amylin-mediated delay of gastric emptying may alter absorption kinetics of orally-dosed medications, including oral contraceptives. Per class precedent, separate administration timing or use of a backup contraceptive method should be considered, particularly during dose escalation.
Reported Research Timeline
01Weeks 1–4 (reported in cited studies): dose escalation; mild GI events possible, especially at faster escalation rates.
02Weeks 4–12 (reported in cited studies): early appetite suppression; 3–6% weight loss apparent.
03Weeks 12–24 (reported in cited studies): continued steady reduction; cardiometabolic markers begin to improve.
04Weeks 24–48 (reported in cited studies): mean reductions of 9.5–20.1% across dose arms; curve not yet plateauing.
Safety Notes
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
Most common Phase 2 adverse events were mild-to-moderate GI symptoms (predominantly nausea) and fatigue.
AE incidence was dose-related and substantially reduced with slower dose escalation.
Phase 1 reported only 2 of 36 eloralintide-treated participants with any GI adverse event across single doses up to 12 mg.
No clinically meaningful changes in vitals, ECG, or laboratory parameters in Phase 1.
Eloralintide is investigational. Safety in pregnancy, lactation, and pediatric populations has not been characterized.
Seek Medical Attention If:
Severe persistent nausea, vomiting, or diarrhea preventing adequate hydration
Signs of pancreatitis (severe abdominal pain radiating to back)
Severe allergic reactions or anaphylaxis
Significant injection-site reactions or abscess
Unexplained tachycardia, syncope, or severe hypoglycemia
Quality Indicators
Verified Marker
AMY1R-selective design
11–12× selectivity for human AMY1R over CTR and AMY3R underlies improved GI tolerability versus non-selective amylin agonists.
Verified Marker
Methylene thioacetal stabilization
Replacement of the native amylin disulfide with a methylene thioacetal bridge improves chemical stability and fibril resistance.
Verified Marker
Once-weekly pharmacokinetics
Terminal half-life of 310–366 hours (≈13–15 days) provides smooth weekly exposure.
Verified Marker
Favorable Phase 2 safety profile
Mild-to-moderate GI events; lower-dose arms had AE rates similar to placebo.
Acceptable Range
Investigational — not commercially available
Phase 3 initiation planned by year-end 2025. Not approved by any regulatory agency.
Acceptable Range
Long-term durability unknown
No data beyond 48 weeks; weight-regain trajectory after discontinuation has not been characterized.
Quality Concern
Gray-market 'research-grade' material
Lilly has not licensed any research-use formulation. Unregulated 'eloralintide' from peptide vendors has no verified identity, purity, or sequence.
Research Citations
- Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept
Briere, D.A., Coskun, T., Cabrera, O., et al., 2025, Molecular Metabolism - Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial
Billings, L.K., et al., 2025, The Lancet - Lilly's selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight
Eli Lilly and Company, 2025, Eli Lilly Investor Press Release - A Study of LY3841136 in Adult Participants With Obesity or Overweight (Phase 2 Monotherapy)
ClinicalTrials.gov, 2024, ClinicalTrials.gov - A Study of Eloralintide (LY3841136) Alone or in Combination With Tirzepatide in Participants With Obesity or Overweight and Type 2 Diabetes (ATTAIN)
ClinicalTrials.gov, 2024, ClinicalTrials.gov - A Single Ascending Dose Study of LY3841136 in Healthy Participants (Phase 1)
ClinicalTrials.gov, 2022, ClinicalTrials.gov - Long acting amylin receptor agonists and uses thereof
Eli Lilly and Company, 2022, United States Patent Application Publication - What to know about eloralintide
Eli Lilly and Company, 2025, Lilly.com Stories
Research Focus
weightLoss, appetiteControl, cardiovascular, metabolic
Verified Vendors Carrying Eloralintide
Frequently Asked Questions
What should researchers watch for with Eloralintide?
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
What should researchers expect over time with Eloralintide?
Weeks 1–4 (reported in cited studies): dose escalation; mild GI events possible, especially at faster escalation rates.
How is Eloralintide typically administered in research?
As reported in cited literature and research-community logs (see Research Citations below) — not a personal dosing recommendation.
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