Eloralintide

Status In clinical development, not approvedBest evidence E2Sources checked 2026-09-17

Eloralintide is an investigational Lilly amylin receptor agonist that produced up to 20.1 percent weight loss at 48 weeks in a 263 person phase 2 trial, under an efficacy estimand rather than a treatment policy one. Its selling point is receptor selectivity meant to reduce nausea, yet phase 2 reported nausea in 64 percent of…

Identity

Sequence: Not disclosed. Lilly has published chain length, bridge chemistry and acylation site but no sequence. Three of the 37 residues are non coded, so a conventional single letter string could not describe the molecule even if the backbone were public.
Formula: C201H319N49O65S2, a figure appearing only on chemical supplier catalogues and in no Lilly paper or registration
Molar mass: 4526.10 Da, a figure appearing only on chemical supplier catalogues and in no Lilly paper or registration
CAS: 2883634-40-8, a registry number appearing only on chemical supplier catalogues and in no Lilly paper or registration

What it is

Eloralintide, development code LY3841136, is an investigational once weekly injectable peptide from Eli Lilly, a synthetic analogue of human amylin, the hormone co secreted with insulin that slows gastric emptying and signals satiation through the hindbrain. It is not approved anywhere and no marketing application has been filed.

Briere 2025 in Molecular Metabolism gives the only public structural description: a main chain of 37 amino acids, the length of native amylin, with three non coded residues at positions 11, 15 and 22, the native disulfide replaced by a methylene thioacetal bridge, and a C20 fatty diacid at lysine 26 that binds albumin and gives a half life of 12.9 to 15.3 days.

Lilly has not published the sequence. Any page printing a clean 37 letter string is printing something the sponsor never released, and with three residues non coded, no letter string could describe the molecule anyway. The molecular weight, formula and CAS number in circulation come only from chemical supplier catalogues, which copy one another.

The selectivity thesis, and how much evidence it has

Amylin receptors form when the calcitonin receptor, CTR, pairs with a receptor activity modifying protein, giving AMY1R and AMY3R, so every amylin analogue engages CTR to some degree. The hypothesis is that CTR engagement in the hindbrain recruits aversive signalling rather than satiation, so sparing it might give the same weight loss with less nausea.

Briere 2025 reports human cAMP EC50 values of 23.9 pM at AMY1R, 253.8 pM at AMY3R and 291.0 pM at CTR, roughly 12 fold more potent at the amylin 1 receptor than at the calcitonin receptor. Cagrilintide, in the same assays, activates all three comparably.

What the margin does not mean is usually lost. Eloralintide reached full agonism at all three human receptors, maximum efficacy above 80 percent at each. It is not a partial agonist or blocker at the calcitonin receptor, only less potent, so at sufficient exposure CTR is engaged.

The tolerability case rests on two rodent experiments. In conditioned taste avoidance in lean rats, eloralintide had an ED50 of 8.9 nmol/kg against 4.2 for cagrilintide, the direction that favours eloralintide. In diet induced obese rats, fat accounted for 80 to 91 percent of the weight it lost against 63 percent for cagrilintide, with significantly less lean mass loss. Both ran in rats, where eloralintide is selective for a different receptor pair: there it is a dual AMY1R and AMY3R agonist selective only against CTR, a different pharmacology from the human one.

Lilly says the rest itself. Its own paper states that “there is no established minimum selectivity threshold to define biologically relevant selectivity,” and offers an alternative: “Differences in potency between eloralintide and cagrilintide could result from differences in PK, particularly the shorter Tmax and half-life of cagrilintide relative to eloralintide.” No head to head human trial exists. Selectivity is the hypothesis phase 3 exists to test, not a demonstrated benefit.

The phase 2 obesity trial

NCT06230523, reported by Billings and colleagues in The Lancet in 2025, randomised 263 adults with obesity or overweight and without type 2 diabetes across seven arms for 48 weeks.

The figures come under the efficacy estimand, which Lilly defines as the efficacy that would have been observed had all randomised participants remained on study intervention for 48 weeks. That is a hypothetical strategy, not a treatment policy result. Quoting 20 percent without it is one of the standard errors about this compound.

On that estimand at week 48: 1 mg minus 9.5 percent, 3 mg minus 12.4, 6 mg minus 17.6, 9 mg minus 20.1, the arm escalated from 6 to 9 mg minus 19.9, the arm escalated through 3 and 6 to 9 mg minus 16.4, and placebo minus 0.4 percent. Placebo lost essentially nothing, where obesity trial placebo arms often lose 2 to 3 percent.

The nausea data undercut the headline

Nausea by arm: 14 percent on placebo, 11 percent at 1 mg, 13 percent at 3 mg, 64 percent at 6 mg, 33 percent at fixed 9 mg, 54 percent in the 6 to 9 mg escalation and 25 percent in the slower escalation. That is not monotonic: the 6 mg arm reported nearly double the rate of the higher fixed 9 mg dose, on 28 and 54 participants respectively.

The highest rates sit at or above the 24 to 31 percent nausea reported for cagrilintide 2.4 mg monotherapy. A compound whose entire thesis is better tolerability reported nausea at or above the compound it was designed to improve on. That is the finding. The low gastrointestinal claim rests on phase 1, where nausea was 8.2 percent over 12 weeks without titration, and 48 weeks of phase 2 qualifies it.

Figures posted but not retrievable

Discontinuation rates by arm, vomiting by arm, serious adverse event counts and responder rates are absent here. The Lancet full text is paywalled and the abstract omits them, while the registry flags results as posted for NCT06230523, so the figures exist and are public. That is a gap in this compilation, not in the evidence.

Heart rate runs backwards to the class

In the 12 week phase 1b study, eloralintide lowered resting pulse dose relatedly: at week 12, minus 3.4 bpm on placebo, minus 8.3 at 6 mg and minus 14.4 bpm at 12 mg. Sigalov and Frishman in Cardiology in Review note the contrast with the heart rate increase associated with GLP-1 receptor agonists. Circulating claims have it inverted. A fall that size is not automatically benign either: the trials exclude bradyarrhythmia and, in the diabetes protocol, a resting pulse below 60 bpm. No amylin receptor agonist has been through a cardiovascular outcomes trial.

What has not reported yet

Five phase 3 studies carrying ENLIGHTEN acronyms are registered, across obesity, type 2 diabetes, sleep apnoea, knee osteoarthritis and obesity persisting on a weekly incretin, 5,615 participants in total. None has reported and the earliest primary completion is January 2028. The acronyms run 1, 2, 3, 4 and 6, so a page citing an ENLIGHTEN-5 is citing nothing.

The phase 2 trial in type 2 diabetes, NCT06603571, enrolled 367 participants and reports at an EASD symposium on 30 September 2026, thirteen days after this entry was source checked. Those results were not public at the time of writing.

What circulates, and why no numbers appear here

Grey market vendors sell vials labelled eloralintide, commonly 1 mg or 10 mg, under research use framing. Whatever is in them is not the sponsor’s investigational product, and with no published sequence nobody can confirm it. There is no lawful compounding route either: not a component of an approved drug, no USP monograph, not on the FDA bulk substances list.

This site does not reproduce the circulating figures for this compound, because the compound is unapproved, the escalation is where the harm sits, and nothing verifies that the vials contain what the label says.

What the record gets wrong

That it is approved or available. It is neither, and no application has been filed anywhere, yet grey market vendors sell it, and at least one supplier catalogue files it under a GLP-1 heading. That is the wrong class entirely: it has no reported activity at the GLP-1, GIP or glucagon receptor.

That it is a cagrilintide analogue. It is not. Different sponsor, different receptor profile, and a half life of roughly 13 to 15 days against 6.6 to 8.1. Cagrilintide is the compound eloralintide was designed to differ from. The conflation propagates into dose claims, with cagrilintide 2.4 mg presented as an eloralintide amount.

That eloralintide with tirzepatide produces figures in the high twenties. Those come from EASD 2026 abstracts released ahead of the meeting, and have not been presented. The only sponsor sourced figure is Lilly stating that eloralintide 3 mg added to tirzepatide 5 mg produced 17 percent weight loss over 16 weeks against 10 percent with tirzepatide alone. That combination, referred to internally as eloraTZP, is a distinct investigational product from eloralintide alone and is not covered by the dosing or safety data in this entry.

Where the class stands

Pramlintide, approved as Symlin in 2005, is the only amylin analogue ever approved, and all its US formulations are discontinued with no approved generic. Cagrilintide reaches regulators only as part of CagriSema, filed with the FDA in December 2025 and not approved. Amycretin has been renamed zenagamtide, so entries comparing eloralintide to both double count one competitor. Which leaves the fact that frames this page: no amylin based product is currently marketed anywhere.

What is not known

Whether receptor selectivity or pharmacokinetics explains the tolerability profile. No trial is designed to separate them, the sponsor names both explanations in the same paragraph, and it expects the question to be settled by other companies’ molecules rather than its own.

What the phase 2 discontinuation rate was. The registry flags results as posted for NCT06230523, so the figure is public, but it was not retrievable for this entry and the abstract does not give it. Vomiting by arm, serious adverse event counts and responder rates sit in the same position.

What happens in type 2 diabetes. Phase 2 trial NCT06603571 in 367 participants reports at an EASD symposium on 30 September 2026, thirteen days after the source check date on this entry. This entry needs revisiting on that date.

Whether any of the phase 2 result replicates at scale. All five ENLIGHTEN phase 3 studies, 5,615 participants combined, have primary completion dates in 2028. Nothing about durability, real world tolerability or long term safety is answerable before then.

What a full agonist at the calcitonin receptor does to bone over time. Bone turnover markers were flat over 12 weeks in 100 people in phase 1b. Nothing longer has been reported, and CTR is the classical bone receptor.

Whether the pulse rate fall matters clinically. The trials exclude bradyarrhythmia and, in the diabetes protocol, a resting pulse below 60 bpm, so the effect has never been observed in the people most likely to be affected by it. No amylin receptor agonist has been through a cardiovascular outcomes trial.

Whether it interacts with oral contraceptives. The interaction study, NCT07808060, has not started and is due in 2027, in a programme whose phase 2 population was 78 percent female. Immunogenicity data have also never been reported, despite reduced immunogenicity risk being a stated design goal.

Doses used in published research

No dose of eloralintide has been established as safe or effective for any indication, because no regulator has approved it and there is no label. What follows is a record of what trials administered, not a schedule.

Phase 2 in obesity, NCT06230523, 263 participants over 48 weeks: single subcutaneous doses of 1, 3, 6 and 9 mg once weekly, plus one arm escalated from 6 to 9 mg and one escalated through 3 and 6 to 9 mg. Placebo was the seventh arm.

Phase 1, NCT05295940: single subcutaneous doses of 0.04, 0.12, 0.4, 1.2, 4 and 12 mg in 48 healthy adults, then 1.2, 3, 6 and 12 mg once weekly for 12 weeks in 100 adults with obesity or overweight, given without escalation within cohorts.

The phase 3 ENLIGHTEN studies do not publish their dose arms in the registry, so the doses carried forward are not public. Note that 12 mg, the dose producing the largest pulse rate reduction in phase 1, is above the 9 mg top dose taken into phase 2.

Compiled from: Billings 2025, The Lancet

No dose has been established as safe or effective for any indication.

Amounts above record what a named source reported administering in a study. They are not a recommendation, not a protocol, and not instructions.

Converting a vial and a syringe into a draw volume is a separate, mechanical question from what amount to use. The reconstitution calculator does that arithmetic for peptide, HCG, and HGH vials.