Eloralintide, formerly known as LY3841136, is Eli Lilly's once-weekly selective amylin receptor agonist. It represents a new class of obesity research compounds that works through the amylin pathway rather than the GLP-1 or GIP receptors targeted by Semaglutide and Tirzepatide. In November 2025, Lilly published Phase 2 data in The Lancet and announced the launch of the Phase 3 ENLIGHTEN programme. This article covers the mechanism, the trial data, and what it means for research procurement.
What is amylin and why does it matter?
Amylin is a pancreatic hormone co-secreted with insulin by beta cells. After meals, amylin circulates to the brainstem and hypothalamus, where it suppresses appetite, delays gastric emptying, and reduces postprandial glucagon secretion. In obesity, amylin signaling may be impaired or desensitised, which has made the amylin receptor an attractive target for weight management research.
The amylin receptor is a heterodimer of the calcitonin receptor (CALCR) and a receptor activity-modifying protein (RAMP). Different RAMP complexes produce different receptor subtypes, and drug developers have spent years trying to design compounds that selectively activate amylin receptors while minimising calcitonin-related effects on bone and calcium metabolism.
Eloralintide mechanism of action
Eloralintide is described as a selective amylin receptor agonist. Preclinical work presented at the American Diabetes Association suggested it lowers body weight with improved gastrointestinal tolerability compared to older non-selective amylin mimetics such as pramlintide and Cagrilintide in rodent models. The proposed mechanism is:
- Enhanced satiety signaling: action in the area postrema and nucleus accumbens reduces food motivation and portion size.
- Slower gastric emptying: contributes to reduced meal size and post-meal glucose excursions.
- Reduced hedonic reward: amylin receptor activation may dampen food cue reactivity in reward circuits.
- No direct insulin stimulation: unlike GLP-1 agonists, amylin agonists do not directly drive glucose-dependent insulin secretion.
Phase 2 trial design and results
The Phase 2 trial (NCT06230523) was a 48-week, randomised, double-blind, placebo-controlled study in 263 adults with obesity or overweight and at least one weight-related comorbidity, without type 2 diabetes. Participants were randomised across seven arms: placebo, 1 mg, 3 mg, 6 mg, 9 mg, 6/9 mg dose escalation, and 3/6/9 mg dose escalation. The mean baseline weight was 109.1 kg.
All Eloralintide cohorts met the primary endpoint of superior body-weight reduction versus placebo at 48 weeks using the efficacy estimand:
| Trial arm | Mean body-weight reduction | Absolute body-weight reduction |
|---|---|---|
| Placebo | -0.4% | -0.2 kg |
| Lowest-dose cohort | -9.5% | -10.2 kg |
| Low-mid dose cohort | -12.4% | -13.3 kg |
| Mid-high dose cohort | -17.6% | -18.7 kg |
| Highest-dose cohort | -20.1% | -21.3 kg |
| Dose-escalation cohort A | -19.9% | -21.0 kg |
| Dose-escalation cohort B | -16.4% | -17.8 kg |
The body-weight reduction curve had not plateaued at 48 weeks for the higher doses, suggesting further loss with longer exposure. Secondary endpoints also showed improvements in waist circumference, blood pressure, lipid profiles, glycaemic markers, and inflammatory markers.
Adverse events reported in published trials
Adverse events reported in the published trial were predominantly mild to moderate gastrointestinal findings and fatigue, which increased across higher-dose cohorts and were reduced with slower dose-escalation study designs. The lowest-dose cohorts reported gastrointestinal event rates similar to placebo. The most commonly reported trial events were nausea, vomiting, diarrhoea, constipation, and injection-site reactions. Unlike GLP-1 agonists, Eloralintide trial data does not show the same pancreatitis signal, although larger Phase 3 data will be needed to fully characterise the adverse event profile.
The ENLIGHTEN Phase 3 programme
Based on the Phase 2 results, Lilly initiated the ENLIGHTEN Phase 3 programme in late 2025 and early 2026. Key trials include:
- ENLIGHTEN-1 (NCT07321886): Eloralintide in 1,980 participants with obesity or overweight without type 2 diabetes. Started February 2026.
- ENLIGHTEN-2 (NCT07282600): Eloralintide in 1,035 participants with obesity or overweight and type 2 diabetes. Started December 2025.
- ENLIGHTEN-6 (NCT07392190): Eloralintide as an add-on in 900 participants with persistent obesity despite treatment with a weekly incretin. Started February 2026.
The ENLIGHTEN-6 trial is particularly interesting because it tests whether amylin agonism can break through body-weight reduction plateaus observed in trial cohorts already receiving GLP-1 or GIP/GLP-1 therapy. If positive, it would position Eloralintide as a complementary mechanism rather than a direct competitor to incretins.
Combination with Tirzepatide
Lilly is also running a separate Phase 2 combination study (NCT06603571) evaluating Eloralintide with Tirzepatide in adults with obesity or overweight and type 2 diabetes. The rationale is mechanistic complementarity: GLP-1/GIP agonists reduce appetite and improve glucose disposal, while amylin agonists suppress food intake via satiety and reward pathways. Early data from this combination are expected in 2026 or 2027.
Comparison with other amylin agonists
Amylin agonism is not a new concept. Pramlintide, a short-acting amylin analogue, was approved for diabetes but had limited uptake due to multiple daily injections and nausea. Novo Nordisk's Cagrilintide, a long-acting amylin/calcitonin dual agonist, has been studied in combination with Semaglutide (CagriSema) and showed additive body-weight reduction as a Phase 2 trial endpoint. Eloralintide's claimed advantage is selectivity: by preferentially activating amylin receptors over calcitonin receptors, it may achieve strong efficacy with an improved tolerability profile.
Implications for research procurement
As Eloralintide moves into Phase 3, demand for research-grade material is increasing for in vitro receptor binding assays, pharmacokinetic modelling, and comparative studies against Cagrilintide and GLP-1 agonists. Research buyers should verify:
- HPLC purity not less than 99%.
- Mass spectrometry confirmation of molecular identity and sequence.
- Endotoxin testing below 0.5 EU/mg for cell-based assays.
- Documented supplier verification and independent batch testing.
Peptx currently lists Eloralintide as a research vial in the factory-direct catalogue and will add further formats as manufacturing and verification are complete. It is sold strictly for research use and is not for human consumption.
What to watch next
The key questions for 2026 and 2027 are: whether the body-weight reduction seen in the highest-dose Phase 2 cohort holds in larger Phase 3 populations; whether the GI tolerability advantage over non-selective amylin agonists is maintained; and whether the combination with Tirzepatide produces additive or synergistic effects. The answers will determine whether Eloralintide becomes a standalone obesity therapy, a combination partner, or both.
References
- Lilly. "Lilly's selective amylin agonist, eloralintide, demonstrated meaningful body-weight reduction and favorable tolerability in a Phase 2 study of adults with obesity or overweight." November 6, 2025.
- Briere DA, et al. "Eloralintide (LY3841136), a selective amylin mimetic, lowered body weight with improved quality of body-weight reduction and GI tolerability in rats compared with cagrilintide." Diabetes 2025;74(Supplement 1):849-P.
- Bhattachar SN, et al. "Eloralintide, a selective, long-acting amylin receptor agonist for obesity: phase 1 proof of concept." Diabetes 2025;74(Supplement 1):882-P.
- ClinicalTrials.gov. NCT06230523, NCT07321886, NCT07282600, NCT07392190, NCT06603571.