Eloralintide: What the Phase 2 Data Actually Showed

For most of the last decade the assumption underneath every serious obesity drug was that a GLP-1 component had to be in the formula somewhere. Semaglutide is a GLP-1 receptor agonist, tirzepatide adds GIP to it, and retatrutide adds glucagon on top of that. Eloralintide has none of them. It is an amylin receptor agonist and nothing else, and in a 48-week phase 2 trial its strongest arms reported a mean bodyweight change of -20% from baseline. That is the kind of number that gets a compound talked about long before anyone reads the paper. The paper is more interesting than the headline, and a good deal more qualified.^[1]

What eloralintide actually is

Eloralintide, also written LY3841136, is an investigational once-weekly amylin receptor agonist from Eli Lilly. Amylin is a hormone the pancreas releases alongside insulin after a meal. It slows gastric emptying and signals through the brain that eating can stop, which is why the class is being studied for weight management at all. Drugs in this class lean on that signal rather than on the incretin pathway semaglutide and tirzepatide work through. What separates eloralintide from earlier amylin compounds is selectivity. The discovery paper in Molecular Metabolism reports that in cell assays it preferentially activated the human AMY1R subtype, roughly 12-fold over the calcitonin receptor and 11-fold over AMY3R, with about 8-fold higher binding affinity for AMY1R than for either. The same paper reports that rats given eloralintide showed less conditioned taste avoidance 72 hours later than rats given cagrilintide, the non-selective amylin analog. The authors connect that selectivity to a hope for gentler gastrointestinal tolerability in people. Whether the hope survives contact with humans is the interesting question, and the phase 2 data gives a partial and slightly awkward answer.^{[1, 2]}

What the phase 2 trial reported

The trial was published in The Lancet in December 2025 and is registered as NCT06230523. It enrolled 263 participants at 46 research centres in the United States between February 2024 and August 2025. Everyone was aged 18 to 75 with a BMI of 30 or higher, or 27 or higher with at least one weight-related comorbidity, and nobody had type 2 diabetes. It ran under an Eli Lilly master protocol for chronic weight management rather than as a standalone study, which is how six eloralintide arms and a placebo arm fitted into one 48-week readout. Participants were randomly assigned to placebo, to one of four constant-dose arms, or to one of two escalation schemes. The primary endpoint was percent change in bodyweight from baseline at 48 weeks. On the efficacy estimand, the mean change ran from -9% in the lowest constant-dose arm to -20% in the highest, with the two escalation arms landing at -20% and -16%, against -0.4% for placebo. Those are group averages across arms holding between 24 and 54 people each, and the confidence intervals overlap heavily, so no single arm should be read as beating another.^{[1, 4, 6]}

The tolerability picture is not a straight line

Nausea was the most common adverse event, and the way it landed across arms is the part worth slowing down for. Reported nausea ran 11%, 13%, 64%, 33%, 54% and 25% across the six eloralintide arms, against 14% on placebo. Read that sequence again. The 64% figure did not come from the strongest arm. It came from a mid-range constant-dose arm, and the arm above it reported 33%. Fatigue behaved similarly, running from 0% to 46% across arms against 12% on placebo, with its peak in an escalation arm rather than the highest constant-dose one. There are two honest readings. One is that dose does not map cleanly onto stomach trouble for this compound. The other is that arms of 24 to 54 people generate noisy percentages, and a trial powered for a bodyweight endpoint is not powered to rank six arms on side effects. The published report does not settle which reading is right. The earlier figures were much smaller. The 12-week phase 1 study, published in Diabetes, Obesity and Metabolism, randomly assigned 100 participants and reported nausea in 8%, diarrhoea in 10% and vomiting in 4% of those receiving eloralintide, with bodyweight reductions of 2.6% to 11.3% across groups. Both sets of numbers are participant incidence, meaning the share of people in an arm who reported the event at least once, so they are the same kind of statistic measured over very different exposures: 12 weeks against 48.^{[1, 3]}

Comparing this with the GLP-1 drugs without fooling yourself

The comparison everyone wants is eloralintide against semaglutide and tirzepatide. It can be made carefully, because all three headline figures are the same measure: mean percent change in bodyweight from baseline. In SURMOUNT-1, 2539 adults received tirzepatide or placebo for 72 weeks, and the mean percentage change in weight was -15.0%, -19.5% and -20.9% across the three tirzepatide groups, against -3.1% on placebo. In STEP 1, 1961 adults received semaglutide or placebo for 68 weeks, and the mean change in bodyweight was -14.9% against -2.4% on placebo. Eloralintide's -20% sits in that territory. The caveats matter more than the headline here. The eloralintide result comes from 48 weeks; the tirzepatide and semaglutide results come from 72 and 68. The eloralintide figure is an efficacy estimand, SURMOUNT-1 reported a treatment-regimen estimand, and STEP 1 reported one that held regardless of discontinuation or rescue intervention, and those choices move the number. The eloralintide trial randomly assigned 263 people; the other two enrolled thousands. One is phase 2, the others phase 3. And no trial has put eloralintide against either drug head to head, so everything above is cross-trial arithmetic over different people. The general rule, which peptide discussion online breaks constantly: only compare statistics that measure the same thing. Percent change in bodyweight against percent change in bodyweight is fair with caveats attached. One trial's share of gastrointestinal events against another trial's share of participants who reported nausea is not a comparison at all, however similar the two percentages look. If you want a head-to-head reading where both sides carry published phase 3 evidence, /compare/tirzepatide-vs-semaglutide is the one that exists on this site, and /compare/cagrilintide-vs-retatrutide is the nearest amylin-adjacent entry.^{[1, 7, 8]}

Where the programme stands now

As of 26 July 2026 a ClinicalTrials.gov search returns 15 interventional eloralintide studies, five of them at phase 3. The largest, NCT07321886, opened on 6 February 2026 and plans 1980 adults with obesity or overweight and without type 2 diabetes, with a main phase of about 75 weeks and a two-year extension for participants with prediabetes. The other phase 3 studies are running in type 2 diabetes, in obstructive sleep apnoea with obesity, in knee osteoarthritis pain, and in people with persistent obesity already on other therapy. Lilly is also studying eloralintide in combination. A completed phase 1 study, NCT06916065, enrolled 188 participants and looked at eloralintide on its own and eloralintide with tirzepatide, and phase 2 work pairs it with macupatide, another Lilly compound. So the company is not treating amylin selectivity purely as a standalone bet. It is also checking whether the mechanism stacks with an incretin drug. None of the combination work has reported results.^{[5, 9, 10]}

What the data does not show

No phase 3 results have been published for eloralintide in any population. Forty-eight weeks is the longest human exposure with published data behind it, so nothing describes what a second or third year looks like. Nothing published describes what happens to bodyweight after the weekly injections stop. The phase 2 trial excluded people with type 2 diabetes, so its numbers do not travel to that group, and the dedicated phase 3 study there is still recruiting. No trial has compared eloralintide with any GLP-1 drug directly. And because the six arms were small, the shape of the relationship between dose and tolerability is a sketch rather than a finding.^{[1, 5, 9]}

Status, and what is sold online

Eloralintide is not approved by the FDA for any use, and it is not approved anywhere else. It exists as an investigational compound inside Eli Lilly's trial programme, and the only people with legitimate access to it are participants in the studies above. Material advertised online under the eloralintide name sits outside that supply chain, so nobody independent is checking its identity, its purity or its contents, and none of the published evidence describes material obtained that way. The compound sheet on this site is at /peptides/eloralintide.^{[5, 9]}

References & sources

1. 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 Dec 6;406(10520):2631-2643. PMID 41207310. Mean percent bodyweight change at 48 weeks (efficacy estimand): 1 mg -9%, 3 mg -12%, 6 mg -18%, 9 mg -20%, 6-9 mg -20%, 3-9 mg -16%, placebo -0.4%. Nausea: 11%, 13%, 64%, 33%, 54%, 25% versus 14% placebo. Fatigue: 0%, 13%, 29%, 43%, 46%, 21% versus 12% placebo.
2. 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 Dec;102:102271. PMCID PMC12640043. Reports preferential activation of human AMY1R (12-fold over the calcitonin receptor, 11-fold over AMY3R) and less conditioned taste avoidance in rats at 72 hours than cagrilintide.
3. 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 Apr;28(4):2651-2660. PMID 41559929. A 12-week multiple ascending dose study in 100 participants; nausea 8%, diarrhoea 10%, vomiting 4%; least squares mean bodyweight reduction 2.6% to 11.3% across groups.
4. ClinicalTrials.gov NCT06230523: A Phase 2, Parallel-Group, Double-Blind Study to Investigate Weight Management With LY3841136 Compared With Placebo in Adult Participants With Obesity or Overweight. Eli Lilly and Company; 263 participants; completed 14 August 2025.
5. ClinicalTrials.gov NCT07321886: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Once Weekly Eloralintide in Adult Participants With Obesity or Overweight, Without Type 2 Diabetes. Eli Lilly and Company; 1980 participants estimated; recruiting; started 6 February 2026; main phase about 75 weeks with a two-year extension for participants with prediabetes.
6. ClinicalTrials.gov NCT06143956: A Master Protocol for a Randomized, Controlled, Clinical Trial of Multiple Interventions for Chronic Weight Management in Adult Participants With Obesity or Overweight (W8M-MC-CWMM). Eli Lilly and Company; the phase 2 framework under which the eloralintide study was run.
7. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022 Jul 21;387(3):205-216. PMID 35658024. Mean percentage change in weight at week 72 was -15.0%, -19.5% and -20.9% across tirzepatide groups versus -3.1% on placebo, in 2539 adults, on the treatment-regimen estimand.
8. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021 Mar 18;384(11):989-1002. PMID 33567185. Mean change in body weight from baseline to week 68 was -14.9% versus -2.4% on placebo, in 1961 adults, on an estimand assessing effects regardless of discontinuation or rescue intervention.
9. ClinicalTrials.gov registry search for eloralintide interventional studies (checked 26 July 2026; 15 studies returned, five of them registered at phase 3, all sponsored by Eli Lilly and Company).
10. ClinicalTrials.gov NCT06916065: A Phase 1, Open-Label, Single and Multiple Dose Study to Investigate the Safety, Tolerability, and Relative Bioavailability of Eloralintide, and Eloralintide With Tirzepatide, in Participants With Overweight or Obesity. Eli Lilly and Company; 188 participants; completed.