At a Glance
| Feature | Detail |
|---|---|
| Full name / code | Eloralintide (LY3841136) — long-acting selective amylin receptor agonist peptide |
| Origin | Eli Lilly; discovery programme published 2025 |
| Mechanism | Preferential agonism at the AMY1R amylin receptor complex (~12-fold over the calcitonin receptor), producing satiety signalling via the brainstem area postrema and reduced food intake |
| Used for | Obesity and overweight — investigational only |
| Route | Once-weekly subcutaneous injection |
| Typical dose range | 1, 3, 6 and 9 mg weekly in phase 2, plus 3–9 mg and 6–9 mg escalation arms |
| Evidence level | Emerging — one 48-week randomised phase 2 trial (n = 263), a multiple-ascending-dose phase 1 (n = 100), a first-in-human phase 1 (n = 48) and preclinical discovery work. No phase 3 results, no approval |
| Regulatory status | Investigational. No FDA, EMA or other approval. Not on any compounding list |
| Anti-doping (WADA 2026) | Non-approved substance — S0, prohibited at all times |
Eloralintide is the most interesting new obesity drug that most people have not heard of, and the reason is mechanistic rather than numerical. Every blockbuster in this field so far pulls incretin levers: GLP-1, GIP, glucagon. Eloralintide pulls a different one — amylin, the hormone co-secreted with insulin that tells the brainstem a meal has arrived.
The honest verdict: 20% mean weight loss over 48 weeks in phase 2 puts eloralintide in tirzepatide territory as monotherapy, achieved through a pathway that does not overlap with the incretins, with a gastrointestinal profile that looks milder in early studies. That combination — comparable efficacy, different receptor, better tolerability — is why Lilly moved to phase 3, and why the obvious next question is what happens when an amylin agonist is combined with an incretin.
The equally honest caveat: this is one phase 2 trial of 263 people. Phase 2 results in obesity have been flattered by phase 3 before, and eloralintide has no long-term safety data, no outcome data and no legitimate route to a patient outside a trial.
How it works
Amylin (islet amyloid polypeptide) is secreted from pancreatic beta cells alongside insulin in roughly a 1:100 molar ratio. Its physiological jobs are to slow gastric emptying, suppress postprandial glucagon and — most relevant here — signal satiation to the brain. It does this in the area postrema of the brainstem, a region outside the blood-brain barrier, which is why a peripherally administered peptide can produce a central satiety effect.
Amylin signalling is unusual in its receptor architecture. There is no dedicated amylin receptor gene. The calcitonin receptor (CTR) pairs with receptor activity-modifying proteins (RAMP1, RAMP2, RAMP3) to form AMY1R, AMY2R and AMY3R, and which complex a drug prefers determines much of its pharmacology.
Eloralintide was designed for selectivity. The discovery paper reports preferential activation of human AMY1R — about 12-fold over the calcitonin receptor and 11-fold over AMY3R — and, importantly, significantly less conditioned taste avoidance in lean rats than cagrilintide, a non-selective amylin agonist (P < 0.05). In diet-induced obese rats it reduced food intake and body weight primarily through fat-mass loss [3].
That is the mechanistic bet: that nausea and aversion in this class track off-target calcitonin-receptor and AMY3R activity, and that selectivity buys tolerability without giving up efficacy. The phase 1 and phase 2 data are consistent with it, and unusually for a tolerability claim, the hypothesis is testable.
Two consequences matter clinically. Amylin agonism and GLP-1 agonism are additive by design rather than duplicative — this is the rationale behind cagrilintide plus semaglutide. And because amylin acts through satiation rather than primarily through delayed gastric emptying, the side-effect profile should differ in character, which is what the trial data show.
What the evidence shows
Phase 2: the 48-week trial
Billings and colleagues (Lancet 2025) enrolled 263 participants from 46 US centres: aged 18–75, BMI ≥30 or ≥27 with at least one weight-related comorbidity, without type 2 diabetes. Mean age 49.0 years, mean body weight 109.1 kg, mean BMI 39.1, 78% female. Randomisation (2:1:1:1:2:1:2) assigned once-weekly subcutaneous placebo or eloralintide at 1, 3, 6 or 9 mg, or escalation schedules of 6–9 mg or 3–9 mg, for 48 weeks.
Mean percent change in body weight at 48 weeks (efficacy estimand):
| Arm | Weight change | 95% CI |
|---|---|---|
| Eloralintide 1 mg (n = 28) | −9% | −12.6 to −6.3 |
| Eloralintide 3 mg (n = 24) | −12% | −14.9 to −9.8 |
| Eloralintide 6 mg (n = 28) | −18% | −20.7 to −14.5 |
| Eloralintide 9 mg (n = 54) | −20% | −22.7 to −17.5 |
| Eloralintide 6–9 mg escalation (n = 24) | −20% | −22.7 to −17.0 |
| Eloralintide 3–9 mg escalation (n = 52) | −16% | −18.6 to −14.1 |
| Placebo (n = 53) | −0.4% | −2.2 to 1.4 |
The commonest adverse events were nausea (11% at 1 mg, 13% at 3 mg, 64% at 6 mg, 33% at 9 mg, 54% in the 6–9 mg arm, 25% in the 3–9 mg arm, 14% on placebo) and fatigue (0%, 13%, 29%, 43%, 46%, 21% and 12% respectively). The investigators reported improvements across waist circumference, blood pressure, lipids, glycaemic measures and inflammatory markers [1].
Two things in that table deserve attention. The dose-response is clean and steep up to 6 mg and then flattens — 9 mg buys about two percentage points over 6 mg. And the nausea figures are not monotonic with dose: 64% at fixed 6 mg against 33% at fixed 9 mg. That pattern usually reflects escalation schedule and small arm sizes rather than the dose itself, and it is one of the questions phase 3 has to resolve.
Phase 1: pharmacokinetics and the tolerability signal
The multiple-ascending-dose phase 1 (Bhattachar, Diabetes Obes Metab 2026) randomised 100 participants, mean BMI 32.6, across five dose cohorts. Exposure was dose-proportional. The commonest treatment-emergent events were decreased appetite (19%), headache (12%) and fatigue (11%); gastrointestinal events were infrequent — diarrhoea 10%, nausea 8%, vomiting 4% — and most events were mild [2].
In a multiple-dose study, that GI profile is substantially gentler than the equivalent early data for incretin agonists, and it is the most distinctive thing about the compound.
The first-in-human trial, reported alongside the discovery work, dosed 48 healthy participants with a mean BMI of 27.5; nine participants on eloralintide reported 16 adverse events, 15 of them mild [3].
Where it sits in the wider amylin field
A 2026 network meta-analysis of six trials (N = 4,642, 12–68 weeks) ranked amylin-based therapies against the incretin standards. High-dose subcutaneous amycretin produced the largest weight reduction (−23.95%), followed by high-dose eloralintide (−18.01%) and high-dose CagriSema (−17.18%), all exceeding semaglutide 2.4 mg (−11.45%) and liraglutide 3.0 mg (−6.4%). Gastrointestinal adverse events were commoner with high-dose amylin-based therapies overall, especially oral amycretin and CagriSema, and only high-dose CagriSema increased discontinuation for adverse events [4].
Network meta-analysis across heterogeneous trials is weaker evidence than a head-to-head, and the ranking is a hypothesis rather than a result. The direction, though, is consistent.
The combination comparator. REDEFINE 5 (Yamauchi, Lancet Diabetes Endocrinol 2026) randomised 331 adults in Japan and Taiwan to cagrilintide-semaglutide or semaglutide alone. Mean weight change at 68 weeks was −18.4% versus −11.9% (treatment difference −6.5 percentage points, P < 0.0001), with discontinuation in 10% versus 6% [7]. That is the benchmark any eloralintide combination programme has to beat. Cagrilintide monotherapy in phase 2 produced 6.0–10.8% weight reduction across 0.3–4.5 mg versus 3.0% on placebo [5], and the first cagrilintide-plus-semaglutide phase 1b established the combination’s feasibility [6].
What is missing
No phase 3 results. No cardiovascular or other outcome data. No published DXA body-composition data — which matters more than people assume, because an amylin satiety mechanism has no obvious reason to spare lean mass and nobody should assume it does without measurement. No data in type 2 diabetes, which the phase 2 trial excluded. And no head-to-head against any incretin.
Dosing
For informational purposes only — this summarises doses used in research and practice; it is not a prescription or individual medical advice.
| Goal | Dose | Route | Frequency / timing | Cycle length | Basis |
|---|---|---|---|---|---|
| Weight loss, best efficacy/tolerability balance in phase 2 | 6 mg weekly | SC | Once weekly | 48 weeks studied | Trial — Billings 2025, PMID 41207310 |
| Maximum studied monotherapy dose | 9 mg weekly | SC | Once weekly | 48 weeks studied | Trial — Billings 2025, PMID 41207310 |
| Escalation schedules tested | 6 mg → 9 mg, or 3 mg → 9 mg over the trial period | SC | Once weekly | 48 weeks | Trial — Billings 2025, PMID 41207310 |
| Lower-dose arms | 1 mg (−9%) or 3 mg (−12%) weekly | SC | Once weekly | 48 weeks | Trial — Billings 2025, PMID 41207310 |
| Practice protocols | None exist. Eloralintide is investigational: no label, no compounding pathway, no practitioner protocol literature | — | — | — | — |
| Grey-market “eloralintide” | Vials have begun appearing from research-chemical vendors; identity, concentration and sterility are unverified and cannot be matched to the clinical material | SC | — | — | Anecdotal — not recommended |
Interpreting the dose-response. The clinically useful reading is that 6 mg captures most of the available effect (−18%) and 9 mg adds about two points (−20%). If phase 3 confirms the pattern, 6 mg is the dose I would expect to see used most, with 9 mg reserved for inadequate response — the same logic that governs tirzepatide 10 versus 15 mg.
Combination logic. Because amylin and incretin receptors are separate systems, the mechanistically obvious protocol is an amylin agonist plus a GLP-1 agonist, which is what CagriSema does and what REDEFINE 5 quantified [7]. No eloralintide combination trial has been published. Anyone combining investigational compounds outside a trial is running an uncontrolled experiment with two unknowns at once.
For injection technique in general, see the peptide injection guide.
What people report: what works and what doesn’t
Eloralintide has never been available outside clinical trials, so there is no meaningful real-world experience base — and reporting that honestly is better than filling the gap. Sources: the trial publications above; the amylin-class reviews [4, 8, 9]; and the open community record on r/Peptides, where discussion is mostly anticipation of supply rather than use.
Reported to work (trial-reported rather than community-reported)
- Reduced appetite, the most frequent treatment-emergent effect in phase 1 at 19% [2] — a drug doing exactly what its mechanism says.
- Dose-dependent weight loss up to 6 mg, consistent and steep [1].
- Improvements in waist circumference, blood pressure, lipids, glycaemic markers and inflammatory markers alongside the weight loss [1].
Mixed or unclear
- The nausea pattern across arms. 64% at fixed 6 mg versus 33% at fixed 9 mg is not a dose-response, and the explanation — escalation schedule, small arms, chance — is unresolved until phase 3 reports [1].
- Fatigue, which rose with dose to 43–46% in the higher arms [1]. Whether that is amylin-specific, a rapid-weight-loss effect, or both is unknown.
- Whether the tolerability advantage survives phase 3 and real-world use. The selectivity hypothesis is reasonable and the preclinical taste-aversion data support it [3], but phase 2 tolerability has looked better than phase 3 tolerability before.
- Whether amylin agonism spares lean mass. No DXA data published. I would not assume a favourable body-composition profile without them.
Reported not to work / disappointing
- Nothing from real use, because there is no real use. Claims circulating about eloralintide results outside the trial setting are not traceable to any verifiable source, and should be read as marketing.
- Grey-market vials sold under the name: the recurring pattern with newly publicised compounds is that early vendor material is mislabelled, under-concentrated, or something else entirely — see peptide sourcing.
What a properly designed trial will need to show: phase 3 confirmation of the 48-week weight loss, body composition by DXA, tolerability over longer exposure, performance in type 2 diabetes, and the result of combining eloralintide with an incretin against that incretin alone. Phase 3 enrolment began after the phase 2 readout; the first of those answers should arrive within two to three years.
Safety and side effects
From the trials. Nausea and fatigue dominate, both dose-related, with the caveat about the non-monotonic nausea pattern noted above. Phase 1 added decreased appetite (19%), headache (12%), and infrequent diarrhoea, nausea and vomiting, nearly all mild [1, 2]. No deaths or dose-limiting safety signals were reported in the published trials.
What is unknown. Everything beyond 48 weeks. Pancreatitis and gallbladder risk — prominent concerns for incretins and plausible with rapid weight loss on any mechanism — have not been characterised for eloralintide. Effects on bone and on calcitonin-receptor-mediated physiology, given the receptor family involved, and effects on lean mass are all open.
A class caution worth carrying over. Pramlintide, the first-generation amylin analogue, carries a boxed warning for severe hypoglycaemia when used with insulin. Until an amylin agonist has been studied alongside insulin, that caution should be assumed to apply.
Practical risk today. The dominant risk is not pharmacological but supply-related. An investigational peptide with published trial results and no legal source is exactly the profile that attracts research-chemical vendors, and a buyer has no way to verify what is in the vial.
Legal and regulatory status
United States. Investigational. No FDA approval for any indication, and no marketing application reported. Eloralintide does not appear on the 503A category 1 list, so compounding pharmacies have no enforcement-discretion pathway for it — see the FDA 2026 compounding update.
European Union and Germany. No EMA authorisation and no clinical availability outside trials.
Sport. A non-approved substance falls under WADA category S0: prohibited at all times, in and out of competition. See peptides and WADA rules.
Trial access. The legitimate route to eloralintide is enrolment in a study. The phase 2 trial was registered as NCT06230523 and completed in August 2025.
How it fits: a second lever, not a replacement
| Semaglutide 2.4 mg | Tirzepatide 15 mg | Eloralintide 9 mg | CagriSema | |
|---|---|---|---|---|
| Mechanism | GLP-1 | GIP + GLP-1 | Amylin (AMY1R-selective) | Amylin + GLP-1 |
| Trial weight loss | ~15% (68 wk) | ~21% (72 wk) | ~20% (48 wk, phase 2) | −18.4% vs semaglutide −11.9% (68 wk) |
| Stage | Approved | Approved | Phase 3 | Phase 3 / filed |
| GI burden | High during titration | High during titration | Low in phase 1, moderate in phase 2 | Highest of the four |
| Combinable with incretins | n/a | n/a | Yes, by design | Already a combination |
| Outcome data | Extensive | Extensive | None | None yet |
The strategic point about eloralintide is not that it might beat tirzepatide. It is that amylin is a separate, additive pathway, which means the ceiling for combination therapy sits higher than the ceiling for any single mechanism. CagriSema’s 6.5 percentage-point advantage over semaglutide alone [7] is the first quantitative demonstration, and a selective amylin agonist with a milder tolerability profile is a better combination partner than a non-selective one.
If you are following this field, the number to watch is not eloralintide’s monotherapy phase 3 result. It is the first eloralintide-plus-incretin trial, and whether the tolerability advantage holds when the two mechanisms are stacked. Watch the body-composition data too: 20% weight loss through a satiety mechanism raises the same lean-mass questions as 20% through an incretin, and the DXA numbers have not been published.
Related Articles
- Tirzepatide: The Dual GIP/GLP-1 Agonist in Full — the current efficacy benchmark.
- Retatrutide vs Semaglutide vs Tirzepatide — how far incretin stacking goes.
- Mazdutide: The GLP-1/Glucagon Dual Agonist Approved in China — the other non-GIP second receptor.
- Native GLP-1 (7-36 Amide): Why “Pure GLP-1” Fails as a Drug — why delivery pharmacology decides which hormones become drugs.
- Preserving Muscle on Semaglutide and Tirzepatide — the open question for every 20%-weight-loss agent.
- Peptide Sourcing: Pharmaceutical-Grade vs Grey Market — why an investigational drug with no legal supply is a sourcing trap.
Frequently asked questions
How much weight did eloralintide cause in its trial?
In the 48-week phase 2 trial (263 adults with obesity or overweight, without diabetes), mean weight change was −9% at 1 mg, −12% at 3 mg, −18% at 6 mg and −20% at 9 mg, versus −0.4% on placebo. A 6–9 mg escalation arm also reached −20%.
Is eloralintide a GLP-1 drug?
No. It activates amylin receptors, not the GLP-1 receptor. Amylin is co-secreted with insulin and signals satiety through the area postrema in the brainstem, which makes eloralintide combinable with GLP-1 agonists rather than redundant with them.
Is eloralintide better tolerated than semaglutide?
Early data suggest less gastrointestinal burden: in the multiple-dose phase 1, nausea was 8% and vomiting 4%. In phase 2 nausea was 33% at 9 mg and 64% in the fixed 6 mg arm versus 14% on placebo, and fatigue was prominent at higher doses. Discovery work showed less conditioned taste avoidance in rats than cagrilintide.
Is eloralintide approved or available?
No. It is an Eli Lilly investigational drug (LY3841136) that entered phase 3 after the phase 2 readout in late 2025. It has no approval anywhere and no legitimate supply; anything sold online under the name is unverified research-chemical material.
How does eloralintide compare with CagriSema?
CagriSema combines cagrilintide (a non-selective amylin agonist) with semaglutide and reached −18.4% at 68 weeks against semaglutide's −11.9% in REDEFINE 5. Eloralintide reached about −20% as monotherapy in phase 2, which is why combining it with an incretin is the interesting question.
What is the difference between selective and non-selective amylin agonists?
Amylin signalling runs through calcitonin receptor complexes — AMY1R, AMY2R, AMY3R — plus the calcitonin receptor itself. Eloralintide preferentially activates AMY1R, roughly 12-fold over the calcitonin receptor. Cagrilintide and pramlintide are non-selective. Selectivity is the hypothesis behind eloralintide's tolerability.
References
- Billings LK, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2025;406(10520):2631-43. PMID: 41207310. https://pubmed.ncbi.nlm.nih.gov/41207310/
- Bhattachar S, et al. Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: phase 1 proof of concept. Diabetes Obes Metab. 2026;28(4):2651-60. PMID: 41559929. https://pubmed.ncbi.nlm.nih.gov/41559929/
- Briere DA, et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: from discovery to clinical proof of concept. Mol Metab. 2025;102:102271. PMID: 41109426. https://pubmed.ncbi.nlm.nih.gov/41109426/
- Kamrul-Hasan ABM, et al. Novel amylin-based therapies for weight management in adults with overweight or obesity without diabetes: a network meta-analysis. Endocrinol Diabetes Metab. 2026;9(3):e70247. PMID: 42175595. https://pubmed.ncbi.nlm.nih.gov/42175595/
- Lau DCW, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021;398(10317):2160-72. PMID: 34798060. https://pubmed.ncbi.nlm.nih.gov/34798060/
- Enebo LB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-48. PMID: 33894838. https://pubmed.ncbi.nlm.nih.gov/33894838/
- Yamauchi T, et al. Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2026;14(6):450-62. PMID: 42009015. https://pubmed.ncbi.nlm.nih.gov/42009015/
- Alhazmi A, et al. Amylin analogs: the next major class of weight loss therapy: a review of experimental data and early-phase clinical trials. Diabetes Obes Metab. 2026;28 Suppl 5:42-50. PMID: 42452898. https://pubmed.ncbi.nlm.nih.gov/42452898/
- Bailey CJ, et al. Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. Peptides. 2026;196:171480. PMID: 41747885. https://pubmed.ncbi.nlm.nih.gov/41747885/
- World Anti-Doping Agency. The 2026 Prohibited List, section S0 (non-approved substances), valid 1 January 2026.
