Eloralintide is an investigational amylin receptor agonist developed for chronic weight management. It extends the action of a pancreatic hormone involved in appetite regulation and has produced substantial weight reduction in a placebo-controlled phase 2 obesity trial. Its development now includes phase 3 studies and a separate combination program with tirzepatide. The engineered peptide preferentially activates AMY1 receptors and produces prolonged circulating exposure, while the clinical studies examine the weight response and tolerability of sustained treatment.
Overview
Eloralintide, previously designated LY3841136, is an engineered analogue of amylin. Briere and colleagues (2025) describe a 37-residue, C-terminally amidated peptide with a stabilized methylene thioacetal bridge and a C20 fatty-diacid side chain attached at lysine 26. These modifications address different problems: the bridge changes chemical stability, while the fatty side chain promotes reversible association with circulating albumin and extends systemic exposure.
Molecular profile
- Development name
- LY3841136 Source
- Molecular form
- Fatty-acid-acylated, amidated amylin analogue Source
- Peptide main chain
- 37 residues Source
- Exposure-extending modification
- C20 fatty diacid at Lys26 through a linker Source
- Bridge
- Methylene thioacetal replacing the native disulfide Source
- Reported receptor preference
- Human AMY1 over AMY3 and calcitonin receptor in assays Source
- Clinical status
- Investigational; phase 3 program ongoing Source
Forms and derivatives
LY3841136
Lilly's earlier development code for eloralintide; the aliases identify the same clinical candidate.
EloraTZP
An investigational combination of eloralintide and tirzepatide. The reported phase 2b study used separate administrations; a proposed co-formulation is part of subsequent development.
The name identifies Lilly's clinical candidate. Its published studies used sponsor-supplied formulations with controlled identity and manufacturing. The compound's structure and clinical evidence should therefore remain connected when interpreting products that use the same name.
Uses and research areas
The principal research area is obesity, including overweight accompanied by weight-related conditions. Researchers have measured body weight, waist circumference, metabolic markers and adverse events over repeated treatment. These outcomes address both the size of the weight response and whether participants can continue treatment long enough to obtain it.
The ENLIGHTEN-1 registry record (2026) documents a confirmatory comparison with placebo in adults without type 2 diabetes. A separate program evaluates eloralintide alongside tirzepatide in people with obesity or overweight and type 2 diabetes. The combination adds amylin receptor activity to tirzepatide's GIP and GLP-1 receptor activity, giving the investigators a way to test whether engaging an additional appetite pathway improves outcomes within the same trial population.
Mechanism of action
How amylin receptors receive a signal
Amylin receptors are formed when the calcitonin receptor associates with a receptor activity-modifying protein, abbreviated RAMP. The RAMP partner changes how the receptor recognizes and responds to hormones. Christopoulos and colleagues (1999) demonstrated this in transfected cells, establishing a molecular explanation for distinct amylin receptor forms. AMY1 and AMY3 refer to complexes containing RAMP1 and RAMP3, respectively.
Eloralintide preferentially activated human AMY1 receptors over human AMY3 and calcitonin receptors in the discovery assays. Selectivity is a comparison of responses over a concentration range; receptor activity can still overlap at higher concentrations. Its clinical significance depends on the tissues exposed, the concentrations reached and how the receptor systems contribute to appetite and adverse effects.
From a circulating hormone to eating behavior
Amylin's appetite effects involve the hindbrain, including the area postrema and neighboring nucleus of the solitary tract. The area postrema can sample blood-borne signals, and nearby neural circuits integrate those signals with information arriving from the digestive tract. In the rat experiment by Lutz and colleagues (1998), lesions in this region attenuated amylin's suppression of food intake. This supplies biological context for appetite-directed amylin analogues, while the human trials determine how much weight changes during sustained exposure.
The receptor assays and feeding experiments measure different links in that explanation. A cell assay can show that a compound activates a defined receptor; eating behavior incorporates the nervous system, physiological feedback and the animal's response to the intervention. Clinical weight measurements add still more influences, including treatment persistence and changes in behavior over months.
Pharmacokinetics
Briere and colleagues (2025) studied single subcutaneous doses in 48 healthy participants. Median time to peak plasma concentration ranged from 72.0 to 132.2 hours. Across the reliably characterized cohorts, geometric mean terminal half-life ranged from 310 to 366 hours, approximately 13–15 days. The two lowest-dose cohorts had insufficient sampling duration for a reliable half-life estimate.
Population: Healthy adults in first-in-human single-dose study; six active participants per cohort; reported range across reliably characterized cohorts. Administration: Subcutaneous administration in the source study. Analyte: Plasma eloralintide.
Briere and colleagues (2025) reported geometric-mean terminal half-lives of 310–366 hours in healthy adults after subcutaneous eloralintide. The model curves begin at the same normalized plasma concentration in the terminal phase and show repeated halving at those rates. The shaded range reflects differences among cohorts; absorption and early distribution are outside the illustration.
Briere DA, Qu H, Lansu K, He MM, Moyers JS, Coskun T, et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept. Molecular Metabolism. 2025;102:102271. doi:10.1016/j.molmet.2025.102271. Briere and colleagues (2025), section 3.2.3; geometric-mean terminal half-lives across the 0.4–12-mg subcutaneous cohorts; Table S11 and Figure S4 cited in the main text.
A slow rise in concentration and a long terminal decline help explain why a weekly interval can be studied despite exposure continuing beyond one week. During repeated treatment, material remaining from earlier administrations contributes to later exposure. Bhattachar and colleagues (2026) found approximately dose-proportional exposure at week 12. Pharmacokinetics describes that exposure; the accompanying weight and adverse-event measurements show the response to it.
Research findings
Early clinical development
Bhattachar and colleagues (2026) randomized 100 adults with obesity or overweight to repeated eloralintide or placebo in a phase 1 study. Weight fell across the active-treatment groups over 12 weeks, alongside measurements of exposure and tolerability. Its short duration and small cohorts served the program's early development purpose: demonstrating sustained exposure and a weight response before undertaking a longer obesity trial.
The 48-week obesity trial
The phase 2 study by Billings and colleagues (2025) enrolled 263 adults without type 2 diabetes at 46 US research centers. Mean weight change at 48 weeks ranged from approximately −9% to −20% across eloralintide groups, compared with −0.4% with placebo. Participants received different treatment amounts and escalation approaches, so the trial examined both the weight response and how the treatment was introduced.
These estimates used an efficacy estimand, which addresses the expected result if randomized participants remained on the study intervention. That question is useful for comparing the drug's effect under sustained treatment. Treatment persistence is an additional clinical question because people who stop an intervention may experience different later outcomes. The distinction becomes particularly relevant when gastrointestinal symptoms or fatigue influence continuation.
Combination with tirzepatide
In Eli Lilly and Company's report (September 30, 2026), the 48-week phase 2b EloraTZP trial included 367 adults with type 2 diabetes. The highest-response combination group had an estimated mean weight reduction of 23.3%, compared with 14.8% for the tirzepatide comparator; reported HbA1c reductions were 2.9 and 2.4 percentage points. Those comparisons were secondary endpoints, and the report presented efficacy-estimand results.
The study administered the two medicines separately. Lilly's planned phase 3 product is a co-formulation, so the completed trial tests the combined treatment strategy while later studies will evaluate the proposed finished product.
Safety and tolerability
Eloralintide remains investigational and is not FDA-approved as of October 13, 2026. The phase 2 obesity paper reported nausea and fatigue among its common adverse events; frequency varied considerably by treatment group. Nausea ranged from 11% to 64% across active groups and was reported by 14% of placebo participants. That uneven pattern is more informative than describing tolerability from the highest-response group's weight result alone.
Combination tolerability also matters. Lilly reported discontinuation because of adverse events in 10.8–27.0% of EloraTZP groups, compared with 2.9% in the tirzepatide comparator group. Gastrointestinal events were more frequent with the combination. These findings make treatment continuation an important part of interpreting the larger weight response.
The available trials do not establish long-term safety in every population, including pregnancy or childhood. Phase 3 studies are intended to characterize benefits and risks in larger groups over longer follow-up. Products sold outside the clinical program have not acquired the trial formulation's evidence through the use of its name.
What the research means
Eloralintide provides clinical evidence that a long-acting amylin-directed treatment can reduce weight substantially without relying on GLP-1 receptor activity in the same molecule. The combination trial adds a more specific finding: adding eloralintide to an incretin strategy can improve weight and glycemic outcomes under the tested conditions, while also increasing tolerability demands.
The next useful results are those that connect these effects to sustained treatment: how many participants remain on therapy, how weight changes over longer follow-up, and whether improvements in metabolic markers translate into fewer clinical complications. Differences in receptor selectivity and half-life give researchers reasons to compare candidates, but clinical comparisons require matching populations, follow-up and methods for handling discontinuation.
FAQs
Is eloralintide approved?
Eloralintide remains investigational as of October 13, 2026. Eli Lilly and Company (2026) describes ongoing phase 3 single-agent studies and planned further combination development.
What does selective amylin receptor agonism mean here?
The term describes stronger activity at particular amylin-receptor complexes in the reported assays. Briere and colleagues (2025) found a preference for human AMY1; receptor response still depends on concentration and assay conditions.
Is EloraTZP another name for eloralintide?
EloraTZP identifies the combination with tirzepatide. Eli Lilly and Company (2026) reports separate administrations in phase 2b and plans a co-formulated product for later development. This distinction connects each result to the preparation tested.
Does the reported average weight loss predict an individual's result?
The phase 2 estimate summarizes a randomized group under a stated efficacy analysis. Billings and colleagues (2025) tested several treatment groups; an individual's response can differ from their group's mean. Continued treatment and tolerability also affect the practical outcome.
Comparisons and related reading
Cagrilintide and petrelintide are other amylin-directed candidates with different chemical designs and receptor profiles. Zenagamtide, also known as amycretin, combines GLP-1 and amylin-family receptor activity in one peptide. Tirzepatide supplies the incretin component of the EloraTZP program. Reading the individual profiles helps connect each clinical result to the molecule and formulation that were studied.
References
Connects the defined molecular modifications and receptor assays with first-in-human exposure measurements.
The repeated-dose phase 1 study characterizes exposure and an early weight response during 12 weeks of treatment.
The longer placebo-controlled trial supplies weight and common-adverse-event findings in adults without type 2 diabetes.
Lilly’s report compares eloralintide plus tirzepatide with tirzepatide alone in type 2 diabetes. The combination produced greater estimated weight reduction, alongside more stopping because of adverse events.
Verifies the confirmatory phase 3 program and its placebo-controlled weight-management objective.
Coexpression experiments explain how calcitonin receptors acquire amylin-receptor pharmacology through RAMP association.
The lesion experiment gives anatomical context for amylin's effects on feeding in rats.
Glossary
- Agonist
- A substance that activates a receptor.
- RAMP
- A receptor activity-modifying protein that changes the pharmacology of the receptor complex.
- AMY1
- An amylin receptor complex containing a calcitonin receptor and RAMP1.
- Terminal half-life
- Time for concentration to halve during the late decline characterized by a terminal elimination rate.
- Efficacy estimand
- A specified treatment-effect question that, in these trials, estimates efficacy under continued study treatment.
- HbA1c
- Glycated hemoglobin, used to summarize preceding average glycemic exposure.