Eloralintide (LY3841136) and the amylin agonists: state of research 2026

What amylin is, and why it sits alongside GLP-1

Amylin is a 37-amino-acid hormone that the beta cells of the pancreas release together with insulin, in roughly the same ratio and at the same moment. Where insulin regulates the uptake of glucose, amylin acts on the speed at which food passes through the gastrointestinal tract and on the signals that mark the end of a meal.

What makes it unusual is the receptor. Amylin has no dedicated receptor with a gene of its own. The amylin receptor only comes into being when the calcitonin receptor couples with a receptor-activity-modifying protein, abbreviated RAMP. Depending on which RAMP protein takes part, the subtypes known in the literature as AMY1, AMY2 and AMY3 arise. That explains why the pharmacology of these substances is harder to characterise than that of a classic receptor agonist, and why selectivity within this class is a research topic in its own right.

The main site of action lies in the area postrema, a region of the brainstem that sits outside the blood-brain barrier and can therefore respond directly to circulating signals. Research shows that amylin receptor components occur there in the same neurons as the leptin receptor. That is the basis for the widely cited hypothesis that amylin partially restores sensitivity to leptin. The hypothesis is supported preclinically and has not been proven in humans.

What matters most for research is that this is a different pathway from the incretin pathway. GLP-1 and GIP act through their own receptors; amylin does not. Two independent routes that both act on food intake make combination research attractive, and that is precisely where the field is currently heading.

Eloralintide: what the phase 2 study showed

Eli Lilly reported the results of a phase 2 study with eloralintide on 6 November 2025. It was a randomised, double-blind, placebo-controlled study over 48 weeks. A total of 263 adults were randomised, with a mean age of 49 years, a mean baseline weight of 109.1 kilograms and a mean BMI of 39.1. The results were presented at ObesityWeek 2025 and published in The Lancet.

The study had six active arms: four fixed doses and two titration schedules. The reported mean weight change after 48 weeks is shown in the table below.

Two things stand out. The first is the dose-response relationship, which rises neatly across the four fixed doses without a plateau at the top end. The second is the side-effect profile. The most frequently reported adverse events were nausea, other mild to moderate gastrointestinal complaints and fatigue, and these occurred more often in the highest dose arms. In the 1 and 3 milligram arms the reporting frequency was close to that of placebo. That is why titration schedules receive so much attention in this field.

Lilly began phase 3 research into eloralintide as monotherapy at the end of 2025 and is also studying the combination with tirzepatide. The latter is the most interesting scientifically, because it brings the amylin pathway and the incretin pathway together in a single treatment question.

The rest of the class: cagrilintide, petrelintide and amycretin

Eloralintide is not alone. In a short time the amylin class has moved from a fringe phenomenon to one of the most crowded areas in metabolic research. The four programmes that matter right now are set side by side below.

Cagrilintide is the furthest advanced, though as part of a combination. In the REDEFINE 1 trial, a weight reduction of 22.7 percent was reported after 68 weeks against 2.3 percent on placebo. In REDEFINE 2, in participants with type 2 diabetes, that was 15.7 percent against 3.1 percent. February 2026 brought a result that illustrates the nuance well. REDEFINE 4 measured 23 percent weight reduction. The prespecified goal of demonstrating non-inferiority to tirzepatide 15 milligrams was not met. A large effect is not automatically a better effect than the existing alternative.

Petrelintide is being developed by Zealand Pharma, since March 2025 together with Roche. The phase 2 trial ZUPREME-1 ran for 42 weeks in participants with obesity without diabetes; the outcome was reported as positive on 5 March 2026. ZUPREME-2, in participants with type 2 diabetes, runs for 28 weeks and will produce results later in 2026. Work is also under way on a fixed combination with CT-388, a GLP-1 and GIP agonist from Roche.

Amycretin from Novo Nordisk follows a different strategy: a single molecule that engages both pathways at once. In a phase 2 trial in participants with type 2 diabetes, published on 25 November 2025, weight reduction was measured over a maximum of 36 weeks. For the injectable form it reached up to 14.5 percent against 2.6 percent on placebo. For the oral form it reached up to 10.1 percent against 2.5 percent. The HbA1c reduction was up to 1.8 percentage points for the injectable form.

Nuance and limitations

The figures above come from different studies with different participants, different durations and different measurement methods. They sit side by side to sketch the state of development, not to suggest a ranking. A direct comparison is only valid within a single study that has tested the compounds head to head, and that kind of research has barely been done in this class.

Phase 2 trials are moreover designed to explore dosing and safety signals, not to establish a definitive effect. Effect sizes from phase 2 regularly come out lower in phase 3, because the study population broadens and dropout patterns differ. The REDEFINE 4 outcome shows that even a good phase 3 result can miss the prespecified goal.

What is still largely missing from the published data on this class is long-term information. Still unknown are what happens after stopping, how the ratio between fat mass and fat-free mass develops, and what the effects are on hard endpoints. For cagrilintide a cardiovascular outcomes trial with around 7000 participants is under way, which has not yet been completed.

Regulation: where these substances stand

None of the four compounds discussed holds a marketing authorisation, neither in the European Union nor outside it. All four are in clinical research. For cagrilintide an application was submitted to the US FDA in December 2025 as part of the combination with semaglutide; at the time of writing that application is still under review.

The class itself is not new. Pramlintide, the first amylin analogue, was approved in the United States in 2005 as an adjunct to mealtime insulin and had to be administered three times a day. In the European Union that compound was never registered. The current generation differs mainly in duration of action: administration once a week instead of at every meal, which substantially changes the research profile.

Because no approval for therapeutic use exists for these compounds anywhere, they fall under residual category S0 of the World Anti-Doping Agency prohibited list. That is relevant to know in research contexts, regardless of whether sport is involved.

Frequently asked questions

What is eloralintide?

Eloralintide, also referred to by the research code LY3841136, is a selective amylin receptor agonist under investigation by Eli Lilly. It is a synthetic peptide designed for once-weekly administration and studied in clinical research in adults with obesity.

How does eloralintide differ from semaglutide or tirzepatide?

Semaglutide acts through the GLP-1 receptor and tirzepatide through both the GLP-1 and the GIP receptor. Eloralintide engages neither and acts through the amylin receptor, which consists of the calcitonin receptor in combination with a RAMP protein. It is therefore a different biological pathway, and that is why the combination of both pathways is being studied.

Has eloralintide been approved?

No. Eloralintide holds no marketing authorisation anywhere in the world. The compound is in phase 3 of clinical research. The same applies to cagrilintide, petrelintide and amycretin.

What does selective mean in selective amylin receptor agonist?

Amylin and calcitonin share receptor components, which means a compound acting on the amylin receptor can also produce calcitonin-like effects. Selectivity means the molecule is designed to engage mainly the amylin receptor while sparing the calcitonin receptor as far as possible. How well that works in practice is one of the questions the ongoing research has to answer.

Does Peplife supply eloralintide?

Peplife supplies research peptides strictly as Research Use Only for laboratory use. Which compounds are available at any given moment is shown in the webshop itself. Research peptides are not intended for use in humans or animals.

Sources

Eli Lilly and Company — phase 2 results eloralintide, press release 6 November 2025 · The Lancet — Eloralintide, a selective amylin receptor agonist for the treatment of obesity, 48-week phase 2 trial · Zealand Pharma — pipeline petrelintide, ZUPREME-1 and ZUPREME-2 · pharmaphorum — phase 2 data amycretin and phase 3 announcement, 25 November 2025 · Drugs.com — registration status and REDEFINE results cagrilintide with semaglutide · Journal of Biological Chemistry — calcitonin and amylin receptor, binding modes and allosteric modulation by RAMP proteins · PubMed — amylin receptor components and the leptin receptor in area postrema neurons

Disclaimer

This article discusses scientific research and is informational only. The compounds mentioned are supplied by Peplife strictly as Research Use Only (RUO) for laboratory research. Nothing here is medical, diagnostic, or dosing advice. Named medicines are cited only to discuss published research.