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 (Billings et al., 2025) and announced plans to start Phase 3 trials, which began as the ENLIGHTEN programme in December 2025 and February 2026. 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 (Mathiesen et al., 2022; Boyle et al., 2018). These effects have 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 (Briere et al., 2025).
Eloralintide mechanism of action
Eloralintide is described as a selective, long-acting amylin receptor agonist (Bhattachar et al., 2026); in cell assays it activated the human amylin 1 receptor about 12 times more potently than the calcitonin receptor (Briere et al., 2025). Preclinical work presented at the American Diabetes Association and published in the same 2025 paper found that in rats it lowered body weight, mainly through fat loss, and caused less conditioned taste avoidance, a rodent measure of gastrointestinal tolerability, than cagrilintide, a non-selective amylin receptor agonist. The proposed mechanism, based on amylin receptor biology, 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.
- Glucose effects through digestion and glucagon: amylin's described glucose-lowering actions are slower gastric emptying and lower post-meal glucagon secretion, whereas GLP-1 agonists also 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, according to Lilly's results release:
| 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 |
Treatment was also associated with improvements in waist circumference, blood pressure, lipid profiles, glycaemic markers, and inflammatory markers, according to Lilly.
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 and fatigue: nausea affected 11% to 13% of the two lowest-dose cohorts against 14% on placebo, rising to 64% in the 6 mg cohort (Billings et al., 2025). 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 a planned 1,980 participants with obesity or overweight without type 2 diabetes. Started February 2026.
- ENLIGHTEN-2 (NCT07282600): Eloralintide in a planned 1,035 participants with obesity or overweight and type 2 diabetes. Started December 2025.
- ENLIGHTEN-6 (NCT07392190): Eloralintide as an add-on in a planned 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 also ran a separate Phase 2 combination study (NCT06603571) evaluating Eloralintide with Tirzepatide in 367 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. In topline results presented at the EASD meeting in September 2026, combinations of the two produced mean body-weight reductions of up to 23.3% at 48 weeks, against 14.8% with tirzepatide alone and up to 12.3% with eloralintide alone, on an efficacy-estimand basis that assumes participants stayed on treatment (Lilly release). These results had not been published in a peer-reviewed journal at the time of this update.
Comparison with other amylin agonists
Amylin agonism is not a new concept. Pramlintide, a short-acting amylin analogue, was approved for diabetes, but its usefulness was limited by a short half-life that requires multiple daily injections (Briere et al., 2025). Novo Nordisk's Cagrilintide, a long-acting, non-selective amylin receptor agonist, has been studied in combination with Semaglutide (CagriSema) and showed additive body-weight reduction as a Phase 2 trial endpoint: in type 2 diabetes, 15.6% at 32 weeks with the combination against 5.1% with semaglutide and 8.1% with cagrilintide alone (Frias et al., 2023). Cagrilintide on its own produced up to 10.8% at 26 weeks in its Phase 2 monotherapy trial (Lau et al., 2021). 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 lab testing.
Peptx supplies Eloralintide as a research compound: Factory Direct kits are available now, and UK single vials have a waitlist. The product page shows current stock. 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 a non-selective amylin agonist, so far shown in rats, is borne out in people; 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
- Bhattachar S, et al. (2026). Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept. Diabetes, Obesity and Metabolism. PubMed 41559929
- Billings LK, et al. (2025). Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. The Lancet. PubMed 41207310
- Boyle CN, et al. (2018). Amylin - Its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity. Molecular Metabolism. PubMed 29203236
- Briere DA, et al. (2025). Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept. Molecular Metabolism. PubMed 41109426
- Frias JP, et al. (2023). Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. The Lancet. PubMed 37364590
- Lau DCW, et al. (2021). Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. The Lancet. PubMed 34798060
- Mathiesen DS, et al. (2022). THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin - physiology and pharmacology. European Journal of Endocrinology. PubMed 35353712