Eloralintide
Eli Lilly's once-weekly selective amylin receptor agonist. Phase 2 trials showed up to 20% weight loss at 48 weeks with favorable tolerability. Phase 3 enrollment began late 2025, and the EloraTZP combination with tirzepatide showed up to 23.3% weight loss in a Phase 2b in obesity plus type 2 diabetes.
What is Eloralintide?
Eloralintide (LY3841136) is a once-weekly, selective amylin receptor agonist developed by Eli Lilly. Amylin is a hormone co-secreted with insulin from pancreatic beta cells that promotes satiety and slows gastric emptying — similar to GLP-1 but through a distinct receptor pathway. Eloralintide's selectivity for the amylin receptor (rather than also activating calcitonin receptors) and its long half-life of approximately two weeks contribute to improved tolerability compared to older amylin analogs like pramlintide. In Phase 2 trials published in The Lancet, eloralintide achieved up to 20% body weight loss at 48 weeks — rivaling tirzepatide — with a side effect profile notable for fatigue rather than the severe nausea typical of GLP-1 drugs. The Phase 3 ENLIGHTEN program began with ENLIGHTEN-2 in type 2 diabetes (NCT07282600, December 2025) and expanded in February 2026 to ENLIGHTEN-1 in obesity without diabetes (NCT07321886), ENLIGHTEN-3 in obstructive sleep apnea (NCT07369011, 800 patients, primary completion March 2028; co-primary measures are body weight change and AHI (apnea-hypopnea index) change at week 64), ENLIGHTEN-4 in knee osteoarthritis pain (NCT07353931), and ENLIGHTEN-6 in people with persistent obesity on a weekly incretin (NCT07392190). Lilly is running two combination tracks. With tirzepatide, the 48-week Phase 2b of 'EloraTZP' (NCT06603571; 367 adults with obesity or overweight and type 2 diabetes) reported in September 2026 up to 23.3% weight loss with eloralintide 9 mg + tirzepatide 15 mg vs 14.8% with tirzepatide 15 mg alone (efficacy estimand), and Lilly plans to start Phase 3 of a co-formulated EloraTZP by the end of 2026. With Lilly's own dual GIPR/GLP-1RA macupatide, two Phase 2 trials are recruiting (NCT07215559 and NCT07589608).
What Eloralintide Is Investigated For
Eloralintide is investigated primarily for weight management in overweight and obese adults, with a pharmacological story built around selective amylin receptor agonism — a distinct pathway from the GLP-1/GIP mechanisms of semaglutide and tirzepatide. The strongest evidence is the Phase 2 trial published in The Lancet (263 participants, 48 weeks, 46 US sites) showing dose-dependent weight loss from 9% at 1 mg to 20% at 9 mg — a magnitude rivaling tirzepatide — along with cardiometabolic improvements across all doses. The Phase 3 ENLIGHTEN-3 program began February 2026 (NCT07369011, 800 patients, primary completion March 2028) and notably tests eloralintide in obesity-plus-OSA with dual co-primary endpoints (body weight change and AHI change at week 64). The honest caveats remain substantial: long-term safety beyond 48 weeks is uncharacterized, no cardiovascular outcomes trial exists, and the combination data are still early — the 48-week EloraTZP Phase 2b with tirzepatide (NCT06603571) showed up to 23.3% weight loss vs 14.8% for tirzepatide 15 mg in obesity plus type 2 diabetes, but with more GI adverse events and higher adverse-event discontinuation in the combination arms, and the parallel combination with Lilly's in-house GIPR/GLP-1RA macupatide (NCT07215559, NCT07589608) is still in Phase 2. The tolerability differentiation claim — fatigue rather than severe nausea — is supported but not absolute, with dose-dependent nausea still present at 6–9 mg arms. Eloralintide is a promising investigational compound, not an available therapy, and FDA approval would not be expected before 2028–2029 if Phase 3 succeeds.
History & Discovery
Eloralintide (LY3841136) was developed at Eli Lilly as a long-acting, selectivity-engineered amylin receptor agonist intended to overcome the limitations of pramlintide — the first-generation amylin analog approved in 2005, whose mealtime dosing burden, mixed amylin/calcitonin receptor activity, and amyloid aggregation tendencies limited adoption. The discovery program is described in a 2025/2026 paper covering the medicinal-chemistry optimization that yielded improved AMY1 receptor selectivity over the calcitonin receptor and a half-life supporting once-weekly dosing. Lilly published Phase 1 proof-of-concept in Diabetes, Obesity and Metabolism, followed by a 48-week Phase 2 trial in The Lancet (263 participants, 46 US sites) showing dose-dependent weight loss reaching approximately 20% at the 9 mg dose. The Phase 3 ENLIGHTEN program began with ENLIGHTEN-2 in type 2 diabetes (NCT07282600) in December 2025 and widened in February 2026 to ENLIGHTEN-1 (obesity without diabetes), ENLIGHTEN-4 (knee osteoarthritis pain), ENLIGHTEN-6 (persistent obesity on a weekly incretin) and ENLIGHTEN-3 (NCT07369011, 800 participants), which has co-primary endpoints of body weight change and apnea-hypopnea index change at week 64 in adults with obesity and moderate-to-severe obstructive sleep apnea, with primary completion targeted March 2028. The combination strategy runs on two tracks. The eloralintide-plus-tirzepatide Phase 1 combination (NCT06916065) completed in January 2026, and the 48-week Phase 2b of the pairing, branded EloraTZP (NCT06603571, 367 adults with obesity or overweight and type 2 diabetes), was presented at EASD on September 30, 2026: up to 23.3% weight loss vs 14.8% with tirzepatide 15 mg alone (efficacy estimand). Lilly said it will start Phase 3 of a co-formulated EloraTZP by the end of 2026. In parallel, Lilly is testing eloralintide with macupatide, its in-house GIPR/GLP-1RA, in two recruiting Phase 2 trials (NCT07215559 and NCT07589608) — stacking complementary metabolic mechanisms inside its own pipeline.
How It Works
Eloralintide mimics amylin, a natural hormone your pancreas releases alongside insulin after meals. Amylin tells your brain you're full and slows down stomach emptying. As a selective amylin receptor agonist, eloralintide activates this satiety signal without triggering related calcitonin receptors — which may explain why it's better tolerated than older amylin drugs.
Eloralintide is a selective agonist of the amylin receptor (AMY1, AMY2, AMY3), which comprises the calcitonin receptor (CTR) complexed with receptor activity-modifying proteins (RAMPs). Unlike pramlintide, eloralintide demonstrates selectivity for amylin receptors over calcitonin receptors, which may contribute to its improved tolerability profile. Amylin receptors in the area postrema and nucleus tractus solitarius mediate satiety signaling, slowed gastric emptying, and suppressed postprandial glucagon secretion. Eloralintide's engineered long half-life (~2 weeks) enables once-weekly subcutaneous dosing. Phase 2 data (263 participants, 48 weeks) showed dose-dependent weight loss: -9% (1 mg), -12% (3 mg), -18% (6 mg), and -20% (9 mg) vs -0.4% placebo, with improvements in waist circumference, blood pressure, lipid profiles, glycemic control, and inflammatory markers. Phase 1 (100 participants, 12 weeks) confirmed dose-proportional pharmacokinetics with 2.6-11.3% weight loss.
Evidence Snapshot
Human Clinical Evidence
Moderate and growing. Phase 2 RCT published in The Lancet (263 participants, 48 weeks, 46 US sites): dose-dependent weight loss from 9% to 20% vs 0.4% placebo, with cardiometabolic improvements across all doses. Phase 1 (100 participants, 12 weeks) published in Diabetes, Obesity and Metabolism confirmed dose-proportional PK and 2.6-11.3% weight loss with good tolerability. Phase 3 ENLIGHTEN program under way: ENLIGHTEN-2 (T2D, NCT07282600) from December 2025; ENLIGHTEN-1 (NCT07321886), ENLIGHTEN-3 (NCT07369011, 800 patients, co-primary obesity + OSA endpoints, primary completion targeted March 2028), ENLIGHTEN-4 (NCT07353931) and ENLIGHTEN-6 (NCT07392190) from February 2026. Combination data: the EloraTZP Phase 2b with tirzepatide (NCT06603571, 367 adults with obesity/overweight and T2D, 48 weeks; EASD September 2026, not yet peer-reviewed) showed up to 23.3% weight loss vs 14.8% with tirzepatide 15 mg and A1C reductions up to 2.9 points (efficacy estimand). Two Phase 2 combination trials with Lilly's GIPR/GLP-1RA macupatide (NCT07215559, NCT07589608) are recruiting.
Animal / Preclinical
Supportive. Discovery-to-clinical-POC paper (PMID: 41109426) describes the preclinical rationale and optimization. Amylin biology is well-established from decades of pramlintide research.
Mechanistic Rationale
Strong. Amylin receptor signaling for satiety and metabolic regulation is well-validated by pramlintide's FDA approval and extensive amylin biology research. Eloralintide's innovation is receptor selectivity and extended half-life, not a novel pathway.
Research Gaps & Open Questions
What the current literature has not yet settled about Eloralintide:
- 01Cardiovascular outcomes — no CVOT has been conducted; whether eloralintide will show MACE reduction comparable to semaglutide is not established.
- 02Long-term safety and efficacy beyond 48 weeks — Phase 3 data will be the first to characterize multi-year exposure.
- 03Body composition effects — sub-studies examining lean mass preservation, bone density, and resistance training mitigation during eloralintide-induced weight loss have not been published.
- 04Combination pharmacology — the EloraTZP Phase 2b (NCT06603571) showed additive weight loss with tirzepatide (up to 23.3% vs 14.8%) but higher adverse-event discontinuation (10.8–27.0% vs 2.9%), and it has not yet been peer-reviewed. Whether the optimized escalation schedule planned for the Phase 3 co-formulation narrows that tolerability gap, and whether the parallel macupatide combination (NCT07215559, NCT07589608) performs differently, are open questions.
- 05Effects in T1D and advanced T2D, where pramlintide has the strongest historical evidence base — eloralintide's selectivity profile may or may not preserve those benefits.
- 06Direct head-to-head comparisons with petrelintide, cagrilintide, and the GLP-1 class.
- 07Response variability and predictors — Phase 2 reported mean weight loss, but the distribution of individual responses, the proportion of high responders versus non-responders, and any baseline predictors (BMI, sex, ethnicity, baseline metabolic markers) of response have not been characterized.
- 08OSA-specific efficacy independent of weight loss — ENLIGHTEN-3's apnea-hypopnea index co-primary endpoint will help disentangle whether amylin signaling contributes to airway physiology beyond the indirect effect of fat mass reduction.
Forms & Administration
Eloralintide is administered as a once-weekly subcutaneous injection. Phase 2 tested doses from 1 mg to 9 mg with various escalation schedules. Slower dose escalation (3 mg → 9 mg) improved tolerability compared to starting at higher doses. It is currently only available through clinical trials.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
There is no clinical prescribing dose because eloralintide is investigational. Phase 2 tested maintenance doses of 1 mg, 3 mg, 6 mg, and 9 mg subcutaneously per week, with weight loss scaling from approximately 9% at 1 mg to approximately 20% at 9 mg over 48 weeks. The 6 mg and 9 mg arms produced higher rates of fatigue and nausea, and slower titration improved tolerability across all arms.
Frequency
Once weekly subcutaneous injection. The engineered ~2-week half-life supports steady-state weekly dosing without requiring more frequent administration.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
Eloralintide is being developed for chronic, indefinite use in obesity, the same paradigm as semaglutide, tirzepatide, and the broader metabolic-peptide class. There is no concept of cycling. Phase 3 protocols will further characterize sustained dosing beyond 48 weeks.
Protocol Notes
Eloralintide is not commercially available and not legally accessible through compounding pharmacies, telehealth, or research-chemical suppliers. Any product offered under the eloralintide or LY3841136 name outside a Lilly-sponsored clinical trial is not the investigational molecule and cannot be assumed to share its sequence, receptor selectivity, or pharmacokinetics. A key feature of eloralintide's design is selectivity for the amylin receptor over the calcitonin receptor — this is sequence-dependent and would not survive arbitrary reproduction by a third party.
Eloralintide is investigational and not approved by the FDA or any other regulatory authority. The doses cited reflect clinical trial protocols rather than prescribing guidance. Use outside an authorized trial carries unquantified risk.
Timeline of Effects
Onset
Phase 1 data showed weight reduction emerging within the 12-week initial dosing period (2.6–11.3% across dose levels). In Phase 2, the weight-loss curve at higher doses began to separate from placebo within the first 4–8 weeks of titration and continued to deepen through the 48-week protocol.
Peak Effect
In the 48-week Phase 2 trial, the weight-loss curve at the 9 mg dose had not clearly plateaued, suggesting peak effect may extend beyond 48 weeks. True peak will be characterized by Phase 3 trials of longer duration. Cardiometabolic improvements (waist circumference, lipids, blood pressure, glycemic control) accrued progressively over the 48-week window.
After Discontinuation
Discontinuation kinetics for eloralintide have not been formally reported. Based on the parallel pharmacology of GLP-1 agonists and the limited follow-up data from cagrilintide trials, substantial weight regain within 6–12 months of cessation should be expected, consistent with the broader principle that pharmacological appetite suppression does not produce durable physiologic remodeling once the drug is withdrawn.
Common Questions
How does eloralintide differ from semaglutide and tirzepatide?
Eloralintide works through the amylin receptor, not GLP-1 or GIP receptors. Amylin is a different satiety hormone co-released with insulin. Because it uses a separate pathway, eloralintide could potentially be combined with GLP-1 drugs for additive effects. Its side effect profile also differs — fatigue is more prominent than nausea.
How does eloralintide compare to pramlintide (Symlin)?
Pramlintide is an older amylin analog that requires multiple daily injections and activates both amylin and calcitonin receptors, contributing to nausea. Eloralintide is selective for the amylin receptor, has a ~2-week half-life enabling once-weekly dosing, and showed notably better tolerability in trials.
When will eloralintide be available?
Eloralintide is in a multi-trial Phase 3 ENLIGHTEN program: ENLIGHTEN-2 in type 2 diabetes began in December 2025, and ENLIGHTEN-1 (obesity without diabetes), ENLIGHTEN-3 (obstructive sleep apnea; NCT07369011, 800 participants, primary completion targeted March 2028), ENLIGHTEN-4 (knee osteoarthritis pain) and ENLIGHTEN-6 (persistent obesity on a weekly incretin) began in February 2026. Lilly also plans to start Phase 3 of the EloraTZP co-formulation with tirzepatide by the end of 2026. If Phase 3 succeeds, the earliest FDA approval would likely be 2028–2029. It is not available outside clinical trials.
What is EloraTZP?
EloraTZP is Lilly's name for eloralintide combined with tirzepatide (Zepbound/Mounjaro). In a 48-week Phase 2b (NCT06603571) of 367 adults with obesity or overweight and type 2 diabetes, presented at EASD in September 2026, the eloralintide 9 mg + tirzepatide 15 mg arm lost an average of 23.3% of body weight vs 14.8% with tirzepatide 15 mg alone, 11.1–12.3% with eloralintide 6–9 mg alone, and 3.0% with placebo, and A1C fell by up to 2.9 percentage points vs 2.4 with tirzepatide (efficacy estimand, which assumes everyone stayed on treatment). The trade-off was tolerability: GI side effects were more frequent in the combination arms, and discontinuation due to adverse events was 10.8–27.0% with EloraTZP vs 2.9% with tirzepatide (16.7% with placebo). The two drugs were given as separate injections in this trial; Lilly plans to start Phase 3 of a single co-formulated product, with an optimized dose-escalation schedule, by the end of 2026.
Is eloralintide's ~20% weight loss really comparable to tirzepatide?
On the headline magnitude alone, yes — the Phase 2 9 mg arm reached approximately 20% mean body weight loss at 48 weeks, which sits in the same range as tirzepatide's SURMOUNT-1 result at 72 weeks. The fair caveats are that Phase 2 was 263 participants versus tirzepatide's much larger Phase 3 dataset, and no head-to-head trial has been run. Eloralintide's interest is partly the magnitude itself and partly that it is achieved through a completely separate receptor pathway, which opens combination strategies that single-pathway drugs cannot offer.
Why does receptor selectivity matter for an amylin drug?
Amylin receptors are heterodimers of the calcitonin receptor (CTR) bound to receptor activity-modifying proteins (RAMPs). Pramlintide activates both the amylin and calcitonin receptors, and that calcitonin-receptor activity is one of the drivers of its nausea and tolerability ceiling. Eloralintide was engineered to favor the AMY1 receptor over the calcitonin receptor, and the better tolerability profile seen in trials is consistent with that design choice — though fatigue at higher doses shows the drug is not free of dose-limiting effects, just different ones.
Who Eloralintide Is NOT For
- •Pregnancy — no human pregnancy data exist; the long half-life and developmental concerns shared by metabolic peptides make use during pregnancy or for at least two months before a planned pregnancy inadvisable.
- •Breastfeeding — no human lactation data; transfer into milk and effects on infants are uncharacterized.
- •Severe gastroparesis or other significant GI motility disorders — amylin receptor agonism slows gastric emptying, which can worsen these conditions.
- •Active or recent pancreatitis — no specific eloralintide pancreatitis signal has been reported, but the precautionary stance applied to other appetite-suppressing peptides extends here pending Phase 3 data.
- •Type 1 diabetes patients on insulin without close monitoring — pramlintide's labeled hypoglycemia risk in T1D is the most relevant class precedent; until eloralintide-specific data exist, similar caution is warranted.
- •Known hypersensitivity to amylin analogs or to formulation excipients.
Drug & Supplement Interactions
Documented drug-interaction data for eloralintide in humans are limited to the Phase 1 and Phase 2 cohorts and have not been the focus of dedicated interaction studies. The class-level interactions known from pramlintide and from broader appetite-suppressing peptides are the best available proxies. Insulin and insulin secretagogues materially raise hypoglycemia risk when combined with amylin agonists, and downward titration of those agents at eloralintide initiation is the expected mitigation. Slowed gastric emptying alters absorption rate and peak concentrations of orally administered medications, with particular relevance for narrow-therapeutic-index agents (warfarin, levothyroxine, oral contraceptives, antiepileptics, and oral antibiotics). The EloraTZP Phase 2b with tirzepatide reported more GI adverse events in the combination arms than with either drug alone, and the Phase 3 co-formulation program will characterize dual-agent pharmacology further; combined use outside a trial is not appropriate. Anyone enrolling in an eloralintide trial while taking chronic medication should disclose all concurrent agents to the trial team.
Safety Profile
Common Side Effects
Cautions
- • Not yet FDA-approved — investigational drug
- • Nausea and fatigue are dose-dependent and more common at higher doses
- • Phase 1 found low GI side effects overall, but Phase 2 showed higher nausea at 6 mg
- • Slower dose escalation significantly improved tolerability
What We Don't Know
Long-term safety beyond 48 weeks has not been studied. Cardiovascular outcomes data is pending. The tirzepatide combination (EloraTZP) has only 48-week Phase 2b safety data, in which GI adverse events and adverse-event discontinuations (10.8–27.0% vs 2.9% with tirzepatide alone) were higher in the combination arms, so the long-term safety of dual therapy is undefined. Effects on bone density, pancreatic health, and long-term metabolic outcomes are unknown.
Legal Status
United States
Eloralintide is not FDA-approved. It is an investigational drug legally administered only to participants in Lilly-sponsored clinical trials, including the Phase 3 ENLIGHTEN program initiated in late 2025, the planned Phase 3 EloraTZP (eloralintide + tirzepatide) program, and Phase 2 combination studies with macupatide. It is not legally available through compounding pharmacies, telehealth platforms, or research-chemical suppliers.
International
No regulatory authority has approved eloralintide. Trial sites operate under the relevant national investigational frameworks but commercial availability does not exist anywhere.
Sports & Competition
Eloralintide is not named on the 2026 or 2027 WADA Prohibited List. Because it has no current approval from any government regulatory health authority for human therapeutic use, it falls under WADA's S0 'Non-approved substances' category, which prohibits drugs in clinical development at all times (in and out of competition). S0 would stop applying only if a regulator approves it. Athletes subject to WADA, USADA, or equivalent codes should treat eloralintide as prohibited.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Eloralintide is available now through specialty compounding pharmacies.
Reality
Eloralintide is an investigational Lilly molecule not approved in any jurisdiction and not legally compoundable in the US. Anything offered under the eloralintide or LY3841136 name outside a sponsored clinical trial is not the investigational product and cannot be assumed to share its sequence or pharmacology.
Myth
Eloralintide produces weight loss without any side effects, unlike GLP-1s.
Reality
Phase 2 data show notably better GI tolerability than GLP-1 agonists in some respects, but fatigue is a prominent dose-dependent side effect (up to ~46% at higher doses), and nausea remains common at the 6 mg and 9 mg arms. Tolerability is improved relative to pramlintide and to GLP-1s on certain axes, but the drug is not side-effect-free.
Myth
Because amylin is 'natural,' eloralintide is safer than synthetic peptides like semaglutide.
Reality
Eloralintide is itself a synthetic engineered analog with sequence modifications for receptor selectivity and a fatty-acid attachment for half-life extension; it is no more or less 'natural' than semaglutide. The relevant safety question is empirical (what do trials show), not derivative of being amylin-derived.
Myth
Eloralintide and pramlintide are the same drug.
Reality
Both target the amylin receptor system, but they differ on every clinically relevant axis: pramlintide is a mealtime injection co-administered with insulin, eloralintide is a once-weekly stand-alone agent; pramlintide co-activates the calcitonin receptor, eloralintide is selective for AMY1; and pramlintide's approved indication is diabetes glycemic control, while eloralintide is being developed primarily for obesity.
Myth
Because eloralintide isn't a GLP-1, it will obviously stack additively with semaglutide or tirzepatide.
Reality
Mechanistic separation is a necessary but not sufficient condition for additive efficacy. Lilly's EloraTZP Phase 2b did show greater weight loss with eloralintide plus tirzepatide (up to 23.3%) than with tirzepatide 15 mg alone (14.8%), but the combination arms also had more GI side effects and more discontinuations due to adverse events. CagriSema's mixed Phase 3 readouts against semaglutide monotherapy are a useful reminder that additivity is empirical, not guaranteed, and has to be confirmed in Phase 3.
Published Research
6 studiesNovel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.
May 2026 network meta-analysis directly comparing amylin-class agents (cagrilintide, petrelintide, eloralintide, amycretin) for weight loss in non-diabetic obesity — the first systematic cross-class comparison ranking eloralintide alongside its peers.
Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies.
Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes.
Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept.
Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.
263 patients, 48 weeks, up to 20% weight loss
Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.
Quick Facts
- Class
- Amylin Receptor Agonist
- Tier
- C
- Evidence
- Emerging
- Safety
- Limited Data
- Updated
- Oct 2026
- Citations
- 6PubMed
Also known as
Tags
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Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.