EloralintideWeight Loss / GLP-1

Eloralintide (LY3841136) is an investigational long-acting amylin receptor agonist developed by Eli Lilly for chronic weight management, given once weekly by subcutaneous injection. What distinguishes it from most compounds in the obesity pipeline is receptor preference: it is engineered to act at the amylin receptor without engaging the GLP-1, GIP or glucagon receptors that drive semaglutide, tirzepatide and retatrutide. It is not approved by the FDA for any use and remains investigational; it is sold here for research purposes only, not as a prescription medicine. Some vendors list it under the brand name "Elora."

Amylin is a hormone co-secreted with insulin from pancreatic beta cells that signals satiety, slows gastric emptying and blunts post-meal glucagon release. Eloralintide reduces appetite and food intake through this pathway, which runs parallel to — rather than overlapping with — incretin receptor agonism.

Structure#

Eloralintide is a 37-amino-acid, C-terminally amidated peptide (C201H319N49O65S2, 4526.10 g/mol, CAS 2883634-40-8) built as a stabilised analog of human amylin. Three engineered changes explain its behaviour:

• Non-standard residues at positions 11, 15 and 22 replace the native amino acids, hardening the

peptide against enzymatic breakdown.

• A methylene thioacetal bridge joins Cys2 and Cys7, in place of the disulfide bond found in

native amylin. Disulfides are chemically labile; the thioacetal is not, which is a large part of why this molecule survives in circulation where native amylin does not.

• Lysine 26 is acylated with two γ-glutamate residues and a saturated 20-carbon diacid. This

fatty-diacid tail binds circulating albumin, and that albumin binding — not the peptide backbone itself — is what stretches the half-life far enough to support once-weekly dosing.

Native human amylin, by contrast, has a half-life of minutes. Essentially every structural decision above exists to convert a rapidly-degraded hormone into a weekly injectable.

Receptor selectivity#

Its receptor profile is preferential rather than absolute, and the distinction matters. In human receptor assays eloralintide favours AMY1R by roughly 12-fold over the calcitonin receptor and 11-fold over AMY3R. That is a meaningful bias, but a ~12-fold margin is not clean separation, and it should not be read as "does not touch the calcitonin receptor." What it does cleanly avoid is the incretin family — there is no GLP-1, GIP or glucagon receptor activity.

Because the gastrointestinal burden of incretin drugs is tied to GLP-1 receptor agonism, an amylin-preferring agonist offers a plausible route to appetite suppression with a different tolerability profile — which is also the rationale for the registered trials pairing it with tirzepatide.

Phase 1 established proof of concept: across dose groups, weight reduction reached roughly 2.6% to 11.3% by week 12, and gastrointestinal adverse events were comparatively infrequent (nausea 8%, vomiting 4%, diarrhoea 10%), with decreased appetite (19%), headache (12%) and fatigue (11%) more common.

The substantive result is the 48-week phase 2 trial (NCT06230523) in 263 adults with obesity, or overweight with at least one obesity-related comorbidity, and without type 2 diabetes. All eloralintide arms met the primary endpoint of superiority to placebo in percent body-weight change:

Results were presented at ObesityWeek 2025 and published simultaneously in The Lancet.

In head-to-head rat work against cagrilintide, the two reduced food intake comparably at matched doses, but eloralintide produced significantly less conditioned taste avoidance — an animal proxy for nausea — and, over chronic dosing, equivalent fat-mass loss with less lean-mass loss. Both findings are preclinical and have not been demonstrated in humans.

Two caveats belong alongside the human numbers. This is a phase 2 trial of 263 participants, not a phase 3 outcomes study, and the comparator was placebo rather than an active incretin agonist — so the figures do not establish how eloralintide performs head-to-head against tirzepatide or semaglutide. Phase 3 and combination trials are registered but had not reported at the time of writing.

In the phase 2 trial the most common adverse events were mild-to-moderate gastrointestinal symptoms and fatigue, occurring more frequently at higher doses; slower dose escalation was associated with lower incidence, and the 1 mg and 3 mg arms showed frequencies similar to placebo. Phase 1 reported decreased appetite, headache and fatigue as the leading events, with nausea and vomiting relatively uncommon for a compound in this therapeutic area.

Because eloralintide remains investigational, there are no long-term human safety data, no approved indication, and no established contraindications or interaction profile. Every figure above comes from company-sponsored trials of limited duration. Research use only — nothing here is therapeutic guidance or a dosing recommendation.