Eloralintide (research code LY3841136) is an investigational, long-acting version of amylin, a hormone the pancreas releases together with insulin after meals. Eli Lilly is developing it as a once-weekly injection for obesity. Unlike cagrilintide, Novo Nordisk’s amylin analogue, it was designed to act mainly on one amylin receptor subtype and much less on the calcitonin receptor (Briere et al., Mol Metab 2025).
The single most important fact: eloralintide is not an approved drug anywhere. Published human data come from two phase 1 trials and one 48-week phase 2 trial of 263 people. A phase 3 program (ENLIGHTEN) began in December 2025, and its estimated primary completion dates are in 2028 (ClinicalTrials.gov).
This page summarizes what the published clinical trials and trial registrations report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Long-acting, selective amylin receptor agonist (lipidated amylin analogue) |
| Developer | Eli Lilly (research code LY3841136) |
| Route | Subcutaneous injection, once weekly |
| Doses studied | Single doses 0.04–12 mg (phase 1); 1.2–12 mg weekly for 12 weeks (phase 1b); 1–9 mg weekly for 48 weeks (phase 2) |
| Half-life | 310–366 h (≈ 12.9–15.3 days) after a single dose, phase 1 |
| Key mechanism fact | In human cell assays, about 12-fold more potent at the AMY1 receptor than at the calcitonin receptor |
| Development stage | Phase 3 (ENLIGHTEN program, started December 2025) |
| US status | Not FDA-approved; investigational only |
| WADA status | Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances), prohibited at all times |
What it is
Amylin is a 37-amino-acid peptide hormone released with insulin from pancreatic beta cells. It slows stomach emptying, limits the rise in glucagon after meals and promotes fullness through actions in the brain (Briere et al., 2025). The first amylin drug, pramlintide, is approved for diabetes but has a short half-life and needs 2–3 injections a day.
Eloralintide is a synthetic amylin analogue built for once-weekly dosing. Lilly’s discovery paper describes its structure as follows (Briere et al., 2025):
- a 37-amino-acid main chain with an amidated C-terminus, including three non-standard amino acids at positions 11, 15 and 22;
- a methylene thioacetal bridge between cysteines 2 and 7, replacing the disulfide bridge of native amylin to improve chemical stability;
- a C20 fatty diacid attached through a linker (two γ-glutamate residues) to the lysine at position 26, which lets the drug bind to albumin in the blood and so extends its half-life.
PubChem lists its formula as C₂₀₁H₃₁₉N₄₉O₆₅S₂ with a molecular weight of about 4,526 g/mol (PubChem).
Mechanism: a “selective” amylin agonist
Amylin receptors are pairs of proteins: the calcitonin receptor (CTR) combined with one of three receptor activity-modifying proteins (RAMPs), giving the AMY1, AMY2 and AMY3 receptors. Calcitonin itself acts mainly on the calcitonin receptor alone.
In human cell assays measuring receptor activation, eloralintide was (Briere et al., 2025):
| Human receptor | Potency (EC50, lower = more potent) | Relative to AMY1 |
|---|---|---|
| AMY1 receptor | 23.9 pM | — |
| AMY3 receptor | 253.8 pM | ≈ 11-fold weaker |
| Calcitonin receptor | 291.0 pM | ≈ 12-fold weaker |
It was still a full agonist at all three receptors, so the selectivity is a matter of degree. In rat receptors the profile differed: eloralintide activated both rat AMY1 and AMY3 much more potently than rat CTR. The authors note there is no established threshold for how much selectivity is biologically meaningful.
How it compares with cagrilintide and amycretin
The three long-acting amylin-based drugs most often discussed together differ mainly in which receptors they hit:
| Feature | Eloralintide | Cagrilintide | Amycretin |
|---|---|---|---|
| Developer | Eli Lilly | Novo Nordisk | Novo Nordisk |
| Receptor profile | Prefers AMY1 over AMY3 and CTR | Nonselective: amylin and calcitonin receptors with similar potency | Single molecule acting on amylin and GLP-1 receptors |
| Half-life | 310–366 h | 159–195 h | See the amycretin page |
| Time to peak level | Median 72–132 h | Median 24–72 h | See the amycretin page |
| Most advanced use | Monotherapy, phase 3 | Mainly with semaglutide (CagriSema) | Weekly injection and daily tablet in development |
Sources: half-life and time-to-peak comparison from Briere et al., 2025; amycretin description from Panou et al., Diabetes Ther 2026, which notes amycretin has been renamed zenagamtide.
In rats, Lilly compared eloralintide directly with cagrilintide. Both reduced food intake similarly, but eloralintide caused less conditioned taste avoidance, a rodent behavior used as a marker of nausea-like discomfort. In a head-to-head study in obese rats, fat made up 80–91% of the weight lost with eloralintide vs 63% with cagrilintide (Briere et al., 2025). These are animal findings from the developer and have not been confirmed in people.
Pharmacokinetics
| Study | Design | Key findings |
|---|---|---|
| Phase 1 single dose (Briere et al., 2025) | 48 participants, single doses 0.04–12 mg | Median time to peak 72–132 h; half-life 310–366 h (12.9–15.3 days) across 0.4–12 mg; total exposure (AUC) proportional to dose; peak level rose less than proportionally |
| Phase 1b multiple dose (Bhattachar et al., Diabetes Obes Metab 2026) | 100 participants, weekly 1.2–12 mg for 12 weeks | Steady-state AUC and peak level dose-proportional; peak-to-trough ratio 1.28–1.38 |
| Phase 2 (ClinicalTrials.gov results) | Weekly 1–9 mg for 48 weeks | Steady-state peak level 322 ng/mL at 1 mg and 3,210 ng/mL at 9 mg |
Key points:
- Very flat levels. A half-life of about two weeks and slow absorption mean blood levels change little across the weekly dosing interval. The developers suggest this may contribute to tolerability, but this has not been tested directly.
- Long washout. With a half-life near 14 days, the drug takes weeks to clear after the last dose.
- Gastric emptying. In the phase 1b trial, higher doses caused a modest slowing of stomach emptying after the first dose, which was no longer seen by week 12 (Bhattachar et al., 2026). This differs from native amylin and pramlintide, which slow gastric emptying; the authors say the finding needs confirmation.
- Kidney and liver impairment. Dedicated phase 1 studies are registered (NCT07426380; NCT07401862), but no results have been published.
Regulatory status
- Not approved. Eloralintide has no FDA or EMA approval; its developers describe it as under development for obesity (Bhattachar et al., 2026). The published trials were funded by Eli Lilly (Billings et al., Lancet 2025).
- Phase 3 program. ClinicalTrials.gov lists five ENLIGHTEN phase 3 trials, all using 64-week percent weight change as a primary endpoint (estimated primary completion 2028):
| Trial | Population | Planned n |
|---|---|---|
| ENLIGHTEN-1 | Obesity or overweight without type 2 diabetes | 1,980 |
| ENLIGHTEN-2 | Obesity or overweight with type 2 diabetes | 1,035 |
| ENLIGHTEN-3 | Obstructive sleep apnea with obesity or overweight | 800 |
| ENLIGHTEN-4 | Knee osteoarthritis pain with obesity or overweight | 900 |
| ENLIGHTEN-6 | Persistent obesity despite weekly incretin treatment | 900 |
- Combination with tirzepatide. Trials of eloralintide given together with tirzepatide are listed as completed, but no results have been posted or published (NCT06916065; NCT06603571).
What the research shows
Phase 1: single doses
In the first-in-human trial, 48 participants (mean BMI 27.5) received a single dose of eloralintide (0.04–12 mg) or placebo. Four weeks after one injection, mean body weight had changed by −2.5% with 4 mg and −4.4% with 12 mg, vs +0.6% with placebo. Lower doses had no significant effect (Briere et al., 2025).
Phase 1b: 12 weeks without dose escalation
This trial randomized 100 adults with overweight or obesity (mean BMI 32.6) to weekly eloralintide or placebo for 12 weeks. Unusually for this drug class, participants started directly on their assigned dose with no gradual dose increase (Bhattachar et al., 2026).
| Weekly dose | n | Placebo-adjusted weight change at 12 weeks |
|---|---|---|
| 1.2 mg | 8 | −2.6% |
| 3 mg | 6 | −8.9% |
| 6 mg | 23 | −8.5% |
| 12 mg | 36 | −11.3% |
| Placebo | 27 | +0.2% (actual change) |
Groups were small and differed in age and sex. The trial was designed to assess safety, not weight loss.
Phase 2: 48-week dose-finding trial
The main efficacy trial randomized 263 adults without diabetes at 46 US centers to weekly placebo or one of six eloralintide regimens for 48 weeks (Billings et al., Lancet 2025). Participants had a BMI of at least 30, or at least 27 with a weight-related condition; mean starting weight was 109.1 kg, mean BMI 39.1, and 78% were women.
Results assume participants stayed on treatment (the efficacy estimand), with ranges from the posted trial results (ClinicalTrials.gov):
| Arm (once weekly) | n | Weight change at 48 weeks (95% CI) | Lost at least 10% of weight |
|---|---|---|---|
| Placebo | 53 | −0.4% (−2.2 to 1.4) | 12.9% |
| 1 mg | 28 | −9.4% (−12.6 to −6.3) | 53.3% |
| 3 mg | 24 | −12.4% (−14.9 to −9.8) | 60.5% |
| 6 mg | 28 | −17.6% (−20.7 to −14.5) | 76.6% |
| 9 mg | 54 | −20.1% (−22.7 to −17.5) | 82.3% |
| 6 mg then 9 mg | 24 | −19.9% (−22.7 to −17.0) | 91.1% |
| 3 → 6 → 9 mg | 52 | −16.5% (−18.6 to −14.1) | 79.2% |
At 9 mg, mean weight loss was 21.3 kg and BMI fell by 7.7 points. Two of the 9 mg arms started at a lower dose and stepped up: 6 mg for 20 weeks then 9 mg; or 3 mg for 4 weeks, 6 mg for 4 weeks, then 9 mg.
Important limits of this evidence:
- Small arms. Each arm had 24–54 people, so differences between arms are imprecise.
- No active comparator. The trial did not test eloralintide against semaglutide or tirzepatide.
- Dropout. In the 1 mg arm, 13 of 28 people did not complete the study, as did 15 of 53 on placebo (ClinicalTrials.gov).
Indirect comparisons
A 2026 network meta-analysis, which compares drugs across separate trials, pooled 6 trials (n=4,642) of amylin-based drugs in people without diabetes. Compared with placebo, high-dose eloralintide reduced body weight by 18.0 percentage points, vs 17.2 for high-dose CagriSema, 24.0 for high-dose injectable amycretin and 11.45 for semaglutide 2.4 mg (Kamrul-Hasan et al., Endocrinol Diabetes Metab 2026). The authors rated the certainty of these comparisons as mostly low or very low, and trial lengths ranged from 12 to 68 weeks, so the ranking is preliminary.
For context, cagrilintide alone produced 6.0–10.8% weight loss after 26 weeks across doses of 0.3–4.5 mg in its phase 2 trial (Lau et al., Lancet 2021). Differences in trial length, population and design make direct comparison with the eloralintide phase 2 trial unreliable.
What is still unknown
- Long-term effects. The longest completed trial lasted 48 weeks. Weight regain after stopping has not been reported.
- Cardiovascular outcomes. No amylin receptor agonist, including eloralintide, has been tested in a cardiovascular outcomes trial (Sigalov & Frishman, Cardiol Rev 2026).
- Body composition and diabetes in humans. The fat-sparing lean mass findings come from rats. Results in type 2 diabetes are awaited from ENLIGHTEN-2.
Side effects and risks
Gastrointestinal effects
Without dose escalation in phase 1b, gastrointestinal events were uncommon: across all eloralintide doses, diarrhea occurred in 9.6%, nausea in 8.2% and vomiting in 4.1%. No one stopped the trial because of them (Bhattachar et al., 2026).
Over 48 weeks in phase 2, nausea was more frequent and clearly dose- and schedule-dependent (Billings et al., 2025; ClinicalTrials.gov):
| Arm | Nausea | Vomiting (participants) | Fatigue |
|---|---|---|---|
| Placebo | 14% | 0 of 53 | 12% |
| 1 mg | 11% | 0 of 28 | 0% |
| 3 mg | 13% | 0 of 24 | 13% |
| 6 mg | 64% | 7 of 28 | 29% |
| 9 mg | 33% | 6 of 54 | 43% |
| 6 mg then 9 mg | 54% | 4 of 24 | 46% |
| 3 → 6 → 9 mg | 25% | 1 of 52 | 21% |
Starting at 3 mg and stepping up produced less nausea than starting at 6 mg. A 2026 review summarized that about 10% of phase 2 participants stopped treatment because of adverse events, and that the trial suggested dose titration improves tolerability, although the best schedule is not known (Alhazmi & le Roux, Diabetes Obes Metab 2026).
Fatigue, mood and appetite
Fatigue was a prominent effect, reported by up to 43–46% of people on 9 mg regimens in phase 2. In the phase 1b trial, decreased appetite (19%), headache (12%) and fatigue (11%) were the most common events. Four participants on 6–12 mg had mood-related events (depressed mood or, in one person, persistent depressive disorder), sometimes with fatigue; the three in the 12 mg group stopped treatment and the events resolved within 2–4 days (Bhattachar et al., 2026). A 2026 review described fatigue, headache and appetite loss as a distinct adverse-event profile compared with GLP-1-based drugs (Panou et al., 2026).
Heart rate
Eloralintide lowers resting heart rate, in contrast to the heart rate increase associated with GLP-1 receptor agonists (Sigalov & Frishman, 2026). In the phase 1b trial, mean pulse fell by 14.4 beats per minute at 12 mg vs 3.4 with placebo after 12 weeks, with no symptomatic bradycardia (slow heart rate) reported (Bhattachar et al., 2026). In phase 2, bradycardia was reported as an adverse event in 3 of 28 people on 6 mg, 3 of 54 on 9 mg and 3 of 52 on the 3 → 6 → 9 mg regimen; sinus bradycardia was reported separately in the 6 mg and 9 mg arms; neither was reported on placebo (ClinicalTrials.gov).
Serious adverse events
In phase 2, serious adverse events occurred in 1–3 participants per arm, including 3 of 53 on placebo, and there were no deaths. Events in eloralintide arms included two acute myocardial infarctions, one thalamic stroke, one case of Guillain-Barré syndrome, one of multiple sclerosis, one report of suicidal ideation (1 mg arm), gallstones and a small-bowel obstruction (ClinicalTrials.gov). The trial was too small to show whether any of these were caused by the drug.
Hair loss (alopecia) was reported in 6 of 54 people on 9 mg vs none on placebo. No laboratory, lipid or ECG safety signal was seen over 12 weeks in phase 1b (Bhattachar et al., 2026).
Products outside clinical trials
Eloralintide is only available legitimately inside Lilly-sponsored trials. Products sold outside trials have not been studied, and their identity, purity, dose and sterility are not verified by any regulator.
Legal status and use in sport
Eloralintide is not named on the WADA Prohibited List. However, the S0 class bans any pharmacological substance not covered elsewhere on the List that has no current approval by any government health authority, explicitly including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an investigational drug, eloralintide falls into that class and is prohibited at all times. Its status could change if a regulator approves it.
Key takeaways
- A once-weekly, AMY1-preferring amylin analogue. Eloralintide is a lipidated amylin analogue from Eli Lilly that acts mainly on the AMY1 receptor, with about 12-fold less activity at the calcitonin receptor in human cell assays.
- Very long half-life. About 13–15 days after a single dose, roughly twice that of cagrilintide.
- Large weight loss on its own in phase 2. The 9 mg dose produced 20.1% mean weight loss at 48 weeks vs 0.4% with placebo, in a trial of 263 people.
- Nausea and fatigue are dose-related. Nausea reached 64% when starting at 6 mg, fatigue reached 43–46% on 9 mg regimens, and stepping up gradually reduced nausea.
- Heart rate drops. Pulse fell by about 14 beats per minute at 12 mg in phase 1b, unlike the rise seen with GLP-1 drugs.
- Still investigational. Phase 3 ENLIGHTEN trials started in late 2025; the drug is not approved and is prohibited in sport under WADA’s S0 class.
Sources
- Briere DA, Qu H, Lansu K, 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. PubMed.
- Bhattachar S, Tham LS, Tidemann-Miller B, 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):2651–2660. PubMed.
- Billings LK, Hsia S, Bays H, 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):2631–2643. PubMed.
- Eli Lilly and Company. A Phase 2, Parallel-Group, Double-Blind Study to Investigate Weight Management With LY3841136 Compared With Placebo in Adult Participants With Obesity or Overweight (NCT06230523), posted results. ClinicalTrials.gov.
- Eli Lilly and Company. ENLIGHTEN phase 3 trial registrations: ENLIGHTEN-1 (NCT07321886), ENLIGHTEN-2 (NCT07282600), ENLIGHTEN-3 (NCT07369011), ENLIGHTEN-4 (NCT07353931), ENLIGHTEN-6 (NCT07392190). ClinicalTrials.gov; ClinicalTrials.gov; ClinicalTrials.gov; ClinicalTrials.gov; ClinicalTrials.gov.
- Eli Lilly and Company. Trial registrations for eloralintide in renal impairment (NCT07426380) and hepatic impairment (NCT07401862), and eloralintide with tirzepatide (NCT06916065, NCT06603571). ClinicalTrials.gov; ClinicalTrials.gov; ClinicalTrials.gov; ClinicalTrials.gov.
- Kamrul-Hasan ABM, Khalil I, Mahajan K, 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. PubMed.
- Alhazmi A, le Roux CW. 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. PubMed.
- Panou T, Gouveri E, Popovic DS, Papanas N. New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus. Diabetes Ther. Published online September 28, 2026. doi:10.1007/s13300-026-01921-0. PubMed.
- Sigalov A, Frishman WH. Cardiometabolic Risk Reduction Through Selective Amylin Receptor Agonism: Emerging Cardiovascular Implications of Eloralintide. Cardiol Rev. Published online September 16, 2026. doi:10.1097/CRD.0000000000001468. PubMed.
- Lau DCW, Erichsen L, Francisco AM, 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):2160–2172. PubMed.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 175663130, Eloralintide. PubChem.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.