Eloralintide
Eli Lilly's once-weekly selective amylin receptor agonist. Phase 2 trials showed up to 20% weight loss at 48 weeks with favorable tolerability. Phase 3 enrollment began late 2025.
What is Eloralintide?
Eloralintide (LY3841136) is a once-weekly, selective amylin receptor agonist developed by Eli Lilly. Amylin is a hormone co-secreted with insulin from pancreatic beta cells that promotes satiety and slows gastric emptying — similar to GLP-1 but through a distinct receptor pathway. Eloralintide's selectivity for the amylin receptor (rather than also activating calcitonin receptors) and its long half-life of approximately two weeks contribute to improved tolerability compared to older amylin analogs like pramlintide. In Phase 2 trials published in The Lancet, eloralintide achieved up to 20% body weight loss at 48 weeks — rivaling tirzepatide — with a side effect profile notable for fatigue rather than the severe nausea typical of GLP-1 drugs. Lilly is also studying eloralintide in combination with tirzepatide, which could push weight loss beyond what either achieves alone.
What Eloralintide Is Investigated For
Eloralintide is investigated primarily for weight management in overweight and obese adults, with a pharmacological story built around selective amylin receptor agonism — a distinct pathway from the GLP-1/GIP mechanisms of semaglutide and tirzepatide. The strongest evidence is the Phase 2 trial published in The Lancet (263 participants, 48 weeks, 46 US sites) showing dose-dependent weight loss from 9% at 1 mg to 20% at 9 mg — a magnitude rivaling tirzepatide — along with cardiometabolic improvements across all doses. The honest caveats are substantial: Phase 3 enrollment only began in late 2025, long-term safety beyond 48 weeks is uncharacterized, no cardiovascular outcomes trial exists, and the combination with tirzepatide that could push efficacy higher is still in Phase 2. The tolerability differentiation claim — fatigue rather than severe nausea — is supported but not absolute, with dose-dependent nausea still present at 6–9 mg arms. Eloralintide is a promising investigational compound, not an available therapy, and FDA approval would not be expected before 2028–2029 if Phase 3 succeeds.
History & Discovery
Eloralintide (LY3841136) was developed at Eli Lilly as a long-acting, selectivity-engineered amylin receptor agonist intended to overcome the limitations of pramlintide — the first-generation amylin analog approved in 2005, whose mealtime dosing burden, mixed amylin/calcitonin receptor activity, and amyloid aggregation tendencies limited adoption. The discovery program is described in a 2025/2026 paper covering the medicinal-chemistry optimization that yielded improved AMY1 receptor selectivity over the calcitonin receptor and a half-life supporting once-weekly dosing. Lilly published Phase 1 proof-of-concept in Diabetes, Obesity and Metabolism, followed by a 48-week Phase 2 trial in The Lancet (263 participants, 46 US sites) showing dose-dependent weight loss reaching approximately 20% at the 9 mg dose. Phase 3 enrollment began in late 2025, and a Phase 2 combination study with tirzepatide is underway as part of Lilly's broader strategy of stacking complementary metabolic mechanisms.
How It Works
Eloralintide mimics amylin, a natural hormone your pancreas releases alongside insulin after meals. Amylin tells your brain you're full and slows down stomach emptying. As a selective amylin receptor agonist, eloralintide activates this satiety signal without triggering related calcitonin receptors — which may explain why it's better tolerated than older amylin drugs.
Eloralintide is a selective agonist of the amylin receptor (AMY1, AMY2, AMY3), which comprises the calcitonin receptor (CTR) complexed with receptor activity-modifying proteins (RAMPs). Unlike pramlintide, eloralintide demonstrates selectivity for amylin receptors over calcitonin receptors, which may contribute to its improved tolerability profile. Amylin receptors in the area postrema and nucleus tractus solitarius mediate satiety signaling, slowed gastric emptying, and suppressed postprandial glucagon secretion. Eloralintide's engineered long half-life (~2 weeks) enables once-weekly subcutaneous dosing. Phase 2 data (263 participants, 48 weeks) showed dose-dependent weight loss: -9% (1 mg), -12% (3 mg), -18% (6 mg), and -20% (9 mg) vs -0.4% placebo, with improvements in waist circumference, blood pressure, lipid profiles, glycemic control, and inflammatory markers. Phase 1 (100 participants, 12 weeks) confirmed dose-proportional pharmacokinetics with 2.6-11.3% weight loss.
Evidence Snapshot
Human Clinical Evidence
Moderate and growing. Phase 2 RCT published in The Lancet (263 participants, 48 weeks, 46 US sites): dose-dependent weight loss from 9% to 20% vs 0.4% placebo, with cardiometabolic improvements across all doses. Phase 1 (100 participants, 12 weeks) published in Diabetes, Obesity and Metabolism confirmed dose-proportional PK and 2.6-11.3% weight loss with good tolerability. Phase 3 enrollment began late 2025. Phase 2 combination study with tirzepatide is underway.
Animal / Preclinical
Supportive. Discovery-to-clinical-POC paper (PMID: 41109426) describes the preclinical rationale and optimization. Amylin biology is well-established from decades of pramlintide research.
Mechanistic Rationale
Strong. Amylin receptor signaling for satiety and metabolic regulation is well-validated by pramlintide's FDA approval and extensive amylin biology research. Eloralintide's innovation is receptor selectivity and extended half-life, not a novel pathway.
Research Gaps & Open Questions
What the current literature has not yet settled about Eloralintide:
- 01Cardiovascular outcomes — no CVOT has been conducted; whether eloralintide will show MACE reduction comparable to semaglutide is not established.
- 02Long-term safety and efficacy beyond 48 weeks — Phase 3 data will be the first to characterize multi-year exposure.
- 03Body composition effects — sub-studies examining lean mass preservation, bone density, and resistance training mitigation during eloralintide-induced weight loss have not been published.
- 04Combination pharmacology with tirzepatide — Phase 2 data will inform whether dual-mechanism therapy yields additive efficacy without unacceptable tolerability cost.
- 05Effects in T1D and advanced T2D, where pramlintide has the strongest historical evidence base — eloralintide's selectivity profile may or may not preserve those benefits.
- 06Direct head-to-head comparisons with petrelintide, cagrilintide, and the GLP-1 class.
Forms & Administration
Eloralintide is administered as a once-weekly subcutaneous injection. Phase 2 tested doses from 1 mg to 9 mg with various escalation schedules. Slower dose escalation (3 mg → 9 mg) improved tolerability compared to starting at higher doses. It is currently only available through clinical trials.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
There is no clinical prescribing dose because eloralintide is investigational. Phase 2 tested maintenance doses of 1 mg, 3 mg, 6 mg, and 9 mg subcutaneously per week, with weight loss scaling from approximately 9% at 1 mg to approximately 20% at 9 mg over 48 weeks. The 6 mg and 9 mg arms produced higher rates of fatigue and nausea, and slower titration improved tolerability across all arms.
Frequency
Once weekly subcutaneous injection. The engineered ~2-week half-life supports steady-state weekly dosing without requiring more frequent administration.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
Eloralintide is being developed for chronic, indefinite use in obesity, the same paradigm as semaglutide, tirzepatide, and the broader metabolic-peptide class. There is no concept of cycling. Phase 3 protocols will further characterize sustained dosing beyond 48 weeks.
Protocol Notes
Eloralintide is not commercially available and not legally accessible through compounding pharmacies, telehealth, or research-chemical suppliers. Any product offered under the eloralintide or LY3841136 name outside a Lilly-sponsored clinical trial is not the investigational molecule and cannot be assumed to share its sequence, receptor selectivity, or pharmacokinetics. A key feature of eloralintide's design is selectivity for the amylin receptor over the calcitonin receptor — this is sequence-dependent and would not survive arbitrary reproduction by a third party.
Eloralintide is investigational and not approved by the FDA or any other regulatory authority. The doses cited reflect clinical trial protocols rather than prescribing guidance. Use outside an authorized trial carries unquantified risk.
Timeline of Effects
Onset
Phase 1 data showed weight reduction emerging within the 12-week initial dosing period (2.6–11.3% across dose levels). In Phase 2, the weight-loss curve at higher doses began to separate from placebo within the first 4–8 weeks of titration and continued to deepen through the 48-week protocol.
Peak Effect
In the 48-week Phase 2 trial, the weight-loss curve at the 9 mg dose had not clearly plateaued, suggesting peak effect may extend beyond 48 weeks. True peak will be characterized by Phase 3 trials of longer duration. Cardiometabolic improvements (waist circumference, lipids, blood pressure, glycemic control) accrued progressively over the 48-week window.
After Discontinuation
Discontinuation kinetics for eloralintide have not been formally reported. Based on the parallel pharmacology of GLP-1 agonists and the limited follow-up data from cagrilintide trials, substantial weight regain within 6–12 months of cessation should be expected, consistent with the broader principle that pharmacological appetite suppression does not produce durable physiologic remodeling once the drug is withdrawn.
Common Questions
Who Eloralintide Is NOT For
- •Pregnancy — no human pregnancy data exist; the long half-life and developmental concerns shared by metabolic peptides make use during pregnancy or for at least two months before a planned pregnancy inadvisable.
- •Breastfeeding — no human lactation data; transfer into milk and effects on infants are uncharacterized.
- •Severe gastroparesis or other significant GI motility disorders — amylin receptor agonism slows gastric emptying, which can worsen these conditions.
- •Active or recent pancreatitis — no specific eloralintide pancreatitis signal has been reported, but the precautionary stance applied to other appetite-suppressing peptides extends here pending Phase 3 data.
- •Type 1 diabetes patients on insulin without close monitoring — pramlintide's labeled hypoglycemia risk in T1D is the most relevant class precedent; until eloralintide-specific data exist, similar caution is warranted.
- •Known hypersensitivity to amylin analogs or to formulation excipients.
Drug & Supplement Interactions
Documented drug-interaction data for eloralintide in humans are limited to the Phase 1 and Phase 2 cohorts and have not been the focus of dedicated interaction studies. The class-level interactions known from pramlintide and from broader appetite-suppressing peptides are the best available proxies. Insulin and insulin secretagogues materially raise hypoglycemia risk when combined with amylin agonists, and downward titration of those agents at eloralintide initiation is the expected mitigation. Slowed gastric emptying alters absorption rate and peak concentrations of orally administered medications, with particular relevance for narrow-therapeutic-index agents (warfarin, levothyroxine, oral contraceptives, antiepileptics, and oral antibiotics). The ongoing Phase 2 combination study with tirzepatide will eventually characterize dual-agent pharmacology, but until those data are public, combined use outside that trial is not appropriate. Anyone enrolling in an eloralintide trial while taking chronic medication should disclose all concurrent agents to the trial team.
Safety Profile
Common Side Effects
Cautions
- • Not yet FDA-approved — investigational drug
- • Nausea and fatigue are dose-dependent and more common at higher doses
- • Phase 1 found low GI side effects overall, but Phase 2 showed higher nausea at 6 mg
- • Slower dose escalation significantly improved tolerability
What We Don't Know
Long-term safety beyond 48 weeks has not been studied. Cardiovascular outcomes data is pending. The combination with tirzepatide is still in Phase 2, so the safety profile of dual therapy is undefined. Effects on bone density, pancreatic health, and long-term metabolic outcomes are unknown.
Legal Status
United States
Eloralintide is not FDA-approved. It is an investigational drug legally administered only to participants in Lilly-sponsored clinical trials, including the Phase 3 program initiated in late 2025 and the ongoing Phase 2 combination study with tirzepatide. It is not legally available through compounding pharmacies, telehealth platforms, or research-chemical suppliers.
International
No regulatory authority has approved eloralintide. Trial sites operate under the relevant national investigational frameworks but commercial availability does not exist anywhere.
Sports & Competition
Eloralintide is not yet listed by name on the WADA Prohibited List, but WADA's S0 category (substances not approved by any government regulatory health authority for human therapeutic use) covers it. As a peptide hormone analog, it would also be expected to fall under S2 once approved. Athletes subject to WADA, USADA, or equivalent codes should treat eloralintide as prohibited in and out of competition.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Eloralintide is available now through specialty compounding pharmacies.
Reality
Eloralintide is an investigational Lilly molecule not approved in any jurisdiction and not legally compoundable in the US. Anything offered under the eloralintide or LY3841136 name outside a sponsored clinical trial is not the investigational product and cannot be assumed to share its sequence or pharmacology.
Myth
Eloralintide produces weight loss without any side effects, unlike GLP-1s.
Reality
Phase 2 data show notably better GI tolerability than GLP-1 agonists in some respects, but fatigue is a prominent dose-dependent side effect (up to ~46% at higher doses), and nausea remains common at the 6 mg and 9 mg arms. Tolerability is improved relative to pramlintide and to GLP-1s on certain axes, but the drug is not side-effect-free.
Myth
Because amylin is 'natural,' eloralintide is safer than synthetic peptides like semaglutide.
Reality
Eloralintide is itself a synthetic engineered analog with sequence modifications for receptor selectivity and a fatty-acid attachment for half-life extension; it is no more or less 'natural' than semaglutide. The relevant safety question is empirical (what do trials show), not derivative of being amylin-derived.
Myth
Eloralintide and pramlintide are the same drug.
Reality
Both target the amylin receptor system, but they differ on every clinically relevant axis: pramlintide is a mealtime injection co-administered with insulin, eloralintide is a once-weekly stand-alone agent; pramlintide co-activates the calcitonin receptor, eloralintide is selective for AMY1; and pramlintide's approved indication is diabetes glycemic control, while eloralintide is being developed primarily for obesity.
Published Research
5 studiesObesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators.
Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes.
Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept.
Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.
263 patients, 48 weeks, up to 20% weight loss
Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.
Quick Facts
- Class
- Amylin Receptor Agonist
- Tier
- C
- Evidence
- Emerging
- Safety
- Limited Data
- Updated
- Apr 2026
- Citations
- 5PubMed
Also known as
Tags
Peptide Families
Related Goals
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.