What Is Eloralintide?
Published Jun 22, 2026 · Updated Oct 15, 2026 · 12 minute read
In the 48-week Phase 2 trial published in The Lancet, adults with obesity lost 9.5% to 20.1% of body weight across doses against 0.4% on placebo, with mostly mild gastrointestinal side effects, taking eloralintide, Eli Lilly’s investigational once-weekly selective amylin receptor agonist, which works through the satiety hormone amylin rather than GLP-1. Phase 3 began in December 2025. It is not approved.
Key Takeaways
- Phase 2, 263 adults with obesity and no diabetes, 48 weeks: 9.5%, 12.4%, 17.6%, and 20.1% mean weight loss on 1, 3, 6, and 9 mg versus 0.4% on placebo. Published in The Lancet in 2025.
- Eloralintide (LY3841136) is a once-weekly injectable that selectively activates amylin receptors. It is not a GLP-1 or GIP drug; amylin is a separate satiety hormone released with insulin.
- The most common adverse events were mild to moderate gastrointestinal symptoms and fatigue, more frequent at higher doses. Serious adverse events were no more common than on placebo in the posted registry results (5% across eloralintide arms vs 6%).
- The Phase 3 ENLIGHTEN program began in December 2025; its largest trial, ENLIGHTEN-1, started in February 2026 with about 1,980 adults and a 64-week primary endpoint. No Phase 3 results have been reported.
- In a 48-week Phase 2b trial in type 2 diabetes, eloralintide plus tirzepatide (EloraTZP) produced up to 23.3% weight loss vs 14.8% on tirzepatide 15 mg alone. Lilly plans Phase 3 trials of a co-formulation by the end of 2026.
- It is investigational and not approved anywhere.
| Eloralintide | |
|---|---|
| Code name | LY3841136 |
| Receptor | Amylin receptors, selective |
| Molecule | Peptide, once-weekly subcutaneous injection |
| Maker | Eli Lilly |
| Stage | Phase 3 (ENLIGHTEN program, started December 2025) |
| Phase 2 result | 20.1% weight loss at 48 weeks on 9 mg vs 0.4% placebo |
| Approved | No |
1. How does eloralintide work?
Amylin is a hormone the pancreas releases together with insulin after a meal. It slows gastric emptying, suppresses glucagon, and signals fullness to the brainstem through its own receptors, a pathway separate from the incretin receptors that semaglutide and tirzepatide act on. Pramlintide, the amylin analogue approved for diabetes in 2005, has to be injected at every meal because it lasts hours; eloralintide is engineered to last a week.
“Selective” is the design claim. Amylin receptors are built from the calcitonin receptor plus an accessory protein, and older amylin analogues such as cagrilintide also activate the bare calcitonin receptor, a related receptor with its own effects on bone and calcium. Eloralintide is described by Lilly as selective for the amylin receptors, meaning it is designed to act much less on that second receptor: in human cell assays it was about 12-fold more potent at the AMY1 amylin receptor than at the calcitonin receptor, so the selectivity is a matter of degree (Briere et al., Mol Metab 2025). That is the mechanistic bet behind its tolerability profile. Whether that selectivity matters clinically is what the Phase 3 program will show.
2. How much weight do people lose on eloralintide?
The Phase 2 trial, NCT06230523, ran at 46 research centres in the US from February 2024 to August 2025 and randomised 263 adults aged 18 to 75 (mean age 49, 78% female, 78% White, mean BMI 39.1) with obesity or overweight and no diabetes to placebo or one of four fixed doses or two escalation schedules for 48 weeks, in a 2:1:1:1:2:1:2 ratio. Average starting weight was 109 kg. The two escalation arms started low and stepped up: 6 mg for 20 weeks then 9 mg for 28 weeks (arm size n=24), or 3 mg for 4 weeks, 6 mg for 4 weeks, then 9 mg for 40 weeks (n=52). The fixed-dose arms ranged from n=24 (3 mg) to n=54 (9 mg), and placebo was n=53. The Lancet’s published efficacy-estimand figures carry confidence intervals: 9 mg produced -20% (95% CI -22.7 to -17.5), 6 mg -18% (-20.7 to -14.5), 3 mg -12% (-14.9 to -9.8), and 1 mg -9% (-12.6 to -6.3), against -0.4% on placebo (-2.2 to 1.4). These round slightly differently from Lilly’s press-release figures used in the chart above (20.1%, 17.6%, 12.4%, 9.5%) because the two sources use different rounding and estimand conventions on the same trial.
- Eloralintide
- Placebo
- Eloralintide
- 9.5%
- Eloralintide
- 12.4%
- Eloralintide
- 17.6%
- Eloralintide
- 20.1%
- Placebo
- 0.4%
Placebo 0.4%. 1 mg 9.5%. 3 mg 12.4%. 6 mg 17.6%. 9 mg 20.1%. Escalation arms: 6/9 mg 19.9%, 3/6/9 mg 16.4%.
Source: Lilly, November 2025; ClinicalTrials.gov NCT06230523
Lilly’s release and the ClinicalTrials.gov results table differ by a tenth of a point on two arms (9.4% and 16.5% in the registry); the chart uses Lilly’s figures. The clean dose-response is the notable feature: each step up in dose produced more loss, and 9 mg reached the same territory as tirzepatide 15 mg did at 72 weeks in SURMOUNT-1 (20.9%), in a shorter trial with a different population. Lilly also reported improvements in waist circumference, blood pressure, lipids, glycemic measures, and inflammatory markers as secondary endpoints, without releasing the numbers; those figures are not yet in the public registry results and are not repeated here. These are separate trials, not a comparison.
The registry’s posted secondary outcomes show responder rates and BMI change alongside the headline weight-loss numbers. At 9 mg, 92.7% of participants reached at least 5% weight loss and 82.3% reached at least 10%, against 31.2% and 12.9% on placebo; the 6/9 mg escalation arm had the highest responder rate of any group, 97.5% at ≥5% and 91.1% at ≥10%. Mean BMI fell by 7.7 points on 9 mg and 7.8 points on the 6/9 mg escalation arm, against 0.2 points on placebo.
3. What are the side effects of eloralintide?
Lilly’s release reports that the most common adverse events were mild to moderate gastrointestinal symptoms and fatigue, seen more frequently in the higher-dose arms, and that rates of these events in the 1 mg and 3 mg arms were similar to placebo. The full per-arm results are posted on ClinicalTrials.gov:
Fixed-dose arms:
| Event | Placebo (n=53) | 1 mg (n=28) | 3 mg (n=24) | 6 mg (n=28) | 9 mg (n=54) |
|---|---|---|---|---|---|
| Nausea | 14% | 11% | 13% | 64% | 33% |
| Vomiting | 0% | 0% | 0% | 25% | 11% |
| Diarrhoea | 9% | 4% | 8% | 36% | 11% |
| Fatigue | 12% | 0% | 13% | 29% | 43% |
| Bradycardia | 0% | 0% | 0% | 11% | 6% |
| Injection site reaction | 6% | 0% | 0% | 0% | 6% |
Escalation arms:
| Event | Placebo (n=53) | 6/9 mg (n=24) | 3/6/9 mg (n=52) |
|---|---|---|---|
| Nausea | 14% | 54% | 25% |
| Vomiting | 0% | 17% | 2% |
| Diarrhoea | 9% | 13% | 17% |
| Fatigue | 12% | 46% | 21% |
| Bradycardia | 0% | 0% | 6% |
| Injection site reaction | 6% | 13% | 8% |
(Nausea and fatigue percentages above are the Lancet’s rounded figures for those two events, which differ slightly from ClinicalTrials.gov’s raw counts for the same arms; the other rows are calculated directly from the registry’s posted counts.) Discontinuation for adverse events was low and not clearly dose-related: 2 of 53 on placebo, 2 of 28 on 1 mg, 0 of 24 on 3 mg, 1 of 28 on 6 mg, 1 of 54 on 9 mg, 0 of 24 on 6/9 mg, and 2 of 52 on 3/6/9 mg. Completion rates ranged from 54% (1 mg) to 89% (9 mg); the 9 mg and 3/6/9 mg arms, the two that ran longest at the top dose, had the highest completion.
Fatigue occurred in up to 46% of an eloralintide arm against 12% on placebo, and bradycardia occurred in up to 11% of an eloralintide arm against 0% on placebo; both will be watched in Phase 3. In the registry results, serious adverse events were reported in 3 of 53 people on placebo and 11 of 210 across the eloralintide arms, and no deaths were reported.
4. What is the ENLIGHTEN program?
ENLIGHTEN-1, NCT07321886, is the largest Phase 3 trial: randomised, double-blind, placebo-controlled, in adults with obesity or overweight (BMI 30, or 27 with a weight-related condition such as high blood pressure, dyslipidemia, sleep apnea, or heart disease) and no diabetes, with four dose arms plus placebo and a primary endpoint of percent weight change at week 64. It started recruiting on February 6, 2026, with an estimated 1,980 participants and a primary completion date estimated for March 2028. The first Phase 3 trial to start was ENLIGHTEN-2, in people with type 2 diabetes, on December 15, 2025. As of October 2026 all five ENLIGHTEN trials are recruiting and none has reported results; their estimated primary completion dates fall between January and June 2028.
ENLIGHTEN-1 is one piece of a larger registered program under the LY3841136 development code. ClinicalTrials.gov lists Phase 3 trials in people with obesity and type 2 diabetes (NCT07282600), obstructive sleep apnea and obesity (NCT07369011), osteoarthritis knee pain and obesity (NCT07353931), and people whose weight has plateaued on a weekly incretin drug (NCT07392190). Earlier-phase studies cover Chinese participants, renal and hepatic impairment, and a Phase 1 study in female participants, alongside two Phase 2 trials pairing eloralintide with Lilly’s investigational macupatide (LY3532226): one in people with type 2 diabetes (NCT07215559) and a Phase 2b trial in people without diabetes (NCT07589608).
The trial that may matter more commercially is the combination with tirzepatide, which Lilly now calls EloraTZP. NCT06603571 is a 48-week Phase 2b study, completed in September 2026, that randomised 367 adults with obesity or overweight and type 2 diabetes across ten arms: three eloralintide-alone doses, five eloralintide-plus-tirzepatide dose pairs, a tirzepatide-alone arm, and placebo. Amylin and incretin drugs work through different receptors, so the hypothesis is additive weight loss without additive gastrointestinal burden, the same logic behind Novo Nordisk’s CagriSema. Lilly reported the results on September 30, 2026, at the EASD meeting, using the efficacy estimand (average starting weight 105.4 kg, average A1C 8.1%) (Lilly, September 2026):
| Arm, 48 weeks | Weight change | A1C change (points) |
|---|---|---|
| Eloralintide 9 mg + tirzepatide 15 mg | -23.3% | -2.9 |
| Eloralintide 6 mg + tirzepatide 10 mg | -19.9% | -2.6 |
| Eloralintide 6 mg + tirzepatide 5 mg | -19.4% | -2.7 |
| Eloralintide 3 mg + tirzepatide 5 mg | -13.2% | -2.2 |
| Tirzepatide 15 mg alone | -14.8% | -2.4 |
| Eloralintide 6 mg alone | -12.3% | -1.4 |
| Eloralintide 9 mg alone | -11.1% | -1.3 |
| Eloralintide 3 mg alone | -8.2% | -1.1 |
| Placebo | -3.0% | -0.3 |
The primary endpoint was each combination against placebo; the comparisons with tirzepatide alone were secondary. Gastrointestinal events, mostly mild or moderate and mainly during dose escalation, were more frequent on the combinations than on either drug alone, and 10.8% to 27.0% of people on the combinations stopped because of adverse events, against 0% to 10.8% on eloralintide alone, 2.9% on tirzepatide alone, and 16.7% on placebo. The two drugs were given as separate injections; Lilly says it will start Phase 3 trials of a co-formulated EloraTZP product, with an optimized escalation schedule, by the end of 2026. No peer-reviewed paper or registry results have been posted yet. If the combination works, eloralintide’s commercial role could be as a partner for Zepbound rather than a rival to it.
5. How does eloralintide compare with the other amylin drugs?
| Eloralintide | Cagrilintide | Petrelintide | |
|---|---|---|---|
| Company | Eli Lilly | Novo Nordisk | Zealand Pharma and Roche |
| Receptor profile | Selective amylin agonist | Amylin and calcitonin receptor agonist | Amylin analogue |
| Best monotherapy result | 20.1% at 48 weeks, 9 mg | Tested mainly in combination as CagriSema | 10.7% at 42 weeks, ZUPREME-1 |
| Stage | Phase 3 | Phase 3 alone; CagriSema filed with FDA December 2025 | Phase 3a started 2026 (Zealand, October 2026) |
| Combination partner | Tirzepatide | Semaglutide | Enicepatide (CT-388) |
The petrelintide and cagrilintide pages cover the other two. For a log, an investigational drug is entered like any other: product, date, milligrams, and site. How GLP-1 tracking works covers what to record.
6. Eloralintide FAQ
How much weight do people lose on eloralintide?
In the 48-week Phase 2 trial, 9.5% on 1 mg, 12.4% on 3 mg, 17.6% on 6 mg, and 20.1% on 9 mg, against 0.4% on placebo. Two escalation arms produced 19.9% (6 then 9 mg) and 16.4% (3, 6, then 9 mg). Average starting weight was 109 kg.
How is eloralintide different from Ozempic or Zepbound?
Different hormone. Semaglutide and tirzepatide act on the incretin receptors GLP-1 and GIP. Eloralintide activates amylin receptors; amylin is released from the pancreas alongside insulin and signals fullness through a separate pathway. That is why Lilly is testing it both alone and combined with tirzepatide.
What are the side effects of eloralintide?
Mild to moderate gastrointestinal symptoms and fatigue, more often at higher doses. ClinicalTrials.gov's posted results list nausea in about 64% of the 6 mg arm, fatigue in about 43% of the 9 mg arm, and a slow heart rate (bradycardia) in up to 11% of the 6 mg arm and 6% of the 9 mg arm. Lilly said rates of these events in the 1 mg and 3 mg arms were similar to placebo.
Is eloralintide the same as cagrilintide?
No, but they are the same class. Cagrilintide is Novo Nordisk's long-acting amylin analogue, combined with semaglutide as CagriSema. Eloralintide is Lilly's selective amylin agonist. Petrelintide, from Zealand Pharma and Roche, is the third amylin drug in Phase 3.
When will eloralintide be approved?
No filing exists. The first Phase 3 trial, ENLIGHTEN-2 in people with type 2 diabetes, started in December 2025, and ENLIGHTEN-1 started in February 2026. All five ENLIGHTEN trials use a 64-week primary endpoint, with estimated primary completion dates between January and June 2028, so Phase 3 data are not expected before 2028. Approval would follow a filing after that.
Did many people drop out of the Phase 2 trial?
Some, but not disproportionately at the higher doses. Only 2 of 53 on placebo, 1 of 54 on 9 mg, and 2 of 52 on the 3/6/9 mg escalation arm discontinued specifically because of an adverse event; the 9 mg and 3/6/9 mg arms had the highest overall completion rates (89% and 88%). The 1 mg arm had the lowest completion (54%), driven mostly by withdrawals and loss to follow-up, not adverse events.
What is EloraTZP?
EloraTZP is Lilly's name for eloralintide combined with tirzepatide. In a 48-week Phase 2b trial of 367 adults with obesity or overweight and type 2 diabetes, the top combination (eloralintide 9 mg plus tirzepatide 15 mg) produced 23.3% average weight loss and a 2.9-point A1C drop, against 14.8% and 2.4 points on tirzepatide 15 mg alone and 3.0% on placebo. Discontinuation for adverse events was higher on the combinations (10.8% to 27.0%) than on tirzepatide alone (2.9%). Lilly plans Phase 3 trials of a co-formulated product by the end of 2026.
7. Sources
References used for this article
- Eli Lilly: Lilly's selective amylin agonist eloralintide demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study (November 2025)
- 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.
- ClinicalTrials.gov: NCT06230523, Phase 2 eloralintide in obesity or overweight
- ClinicalTrials.gov: NCT07321886, ENLIGHTEN-1 Phase 3
- ClinicalTrials.gov: NCT06603571, eloralintide with tirzepatide in obesity and type 2 diabetes
- Eli Lilly investor relations: Phase 2 topline results release (November 2025)
- Billings LK 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 (PubMed 41207310).
- Eli Lilly: Lilly's EloraTZP (combination of eloralintide and tirzepatide) delivered greater weight loss and A1C reduction vs. tirzepatide 15 mg in adults with obesity and type 2 diabetes (September 30, 2026)
- ClinicalTrials.gov: NCT07282600, ENLIGHTEN-2 Phase 3 in obesity or overweight with type 2 diabetes
- ClinicalTrials.gov: NCT07215559, Phase 2 macupatide and eloralintide in obesity and type 2 diabetes
- ClinicalTrials.gov: NCT07589608, Phase 2b macupatide and eloralintide in obesity without type 2 diabetes
- Briere DA et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: from discovery to clinical proof of concept. Mol Metab 2025 (PubMed 41109426).
- Zealand Pharma company announcement No. 54/2026: ZUPREME-2 topline results and start of the petrelintide Phase 3a program (October 7, 2026)
- Novo Nordisk: Novo Nordisk files for FDA approval of CagriSema (December 18, 2025)