Amylin Agonist

VialTalk's catalog lists this compound as "Amylin Agonist". The vendor listings attached to it name eloralintide (Eli Lilly code LY3841136), a long-acting amylin receptor agonist built to favour one amylin receptor subtype. Researchers are interested because amylin acts through a hormone system separate from GLP-1, and early trials report substantial weight loss; gastrointestinal effects were infrequent in Phase 1 but more common in some Phase 2 arms. This monograph covers its identity, receptor pharmacology, the published evidence and its gaps.

Chemical identity and structure

Eloralintide is a synthetic peptide analogue of amylin. Amylin is a hormone released from pancreatic beta cells together with insulin [1][6]. PubChem gives the molecular formula C201H319N49O65S2 and a molecular weight of about 4526 daltons [7]. ChEMBL lists its highest clinical phase as 2 at indexing [8]; Phase 3 studies are now registered [11][12][13]. Reviews group it with long-acting amylin agents made possible by lipidation and reversible albumin binding [5].

Mechanism of action

Native amylin slows gastric emptying, suppresses glucagon secretion and promotes satiation through the central nervous system [5][6]. Amylin-based drugs differ in which receptors they activate. Some are selective for amylin receptors. Others, such as cagrilintide, also activate the calcitonin receptor (CTR) [5].

• Selectivity (cell assays). In cells engineered to express single receptors, eloralintide activated the human amylin 1 receptor (AMY1R) about 12-fold more strongly than CTR and about 11-fold more strongly than the amylin 3 receptor (AMY3R) [1]. In rat receptors, AMY1R and AMY3R were both activated more potently than CTR [1], so rodent results do not map directly onto human pharmacology.
• Why selectivity matters. One review proposes that CTR engagement, drug exposure over time and which brain circuits are recruited may decide whether reduced eating reflects normal satiation or an aversive signal such as nausea [5]. This is a hypothesis. It has not been settled.
• An independent group used eloralintide as the selective-AMY1R comparator for new amylin agonists [10]. That is a reference use, not independent efficacy evidence.

What the research shows

Cell / in vitro. The receptor-selectivity profile described above [1].

Animal.

• In lean rats, eloralintide caused significantly less conditioned taste avoidance than cagrilintide (p < 0.05). Taste avoidance is a rodent measure of aversive or malaise-like effects [1].
• In diet-induced obese (DIO) rats, it reduced food intake and body weight, with larger effects at higher exposure, mainly through fat-mass loss [1].
• In a Lilly-sponsored conference abstract, eloralintide combined with tirzepatide in DIO rats reduced food intake, body weight and fat mass more than either agent alone. This held both for combined use from the start and for add-on use [9].

Human.

• Phase 1, single-ascending-exposure study (48 healthy participants). 16 adverse events occurred in 9 eloralintide-treated participants, and 15 of the 16 were mild. Four gastrointestinal events occurred in two participants, including one moderate vomiting event. At week 4, body weight fell in the cohorts with the highest single exposure (−2.5% and −4.4%) compared with +0.6% on placebo [1].
• Phase 1, multiple-ascending-exposure study (100 participants with obesity or overweight, 12 weeks).

- Drug exposure increased proportionally across the escalating cohorts [2].
- The most common treatment-emergent adverse events were decreased appetite (19%), headache (12%), fatigue (11%) and COVID-19 (11%) [2].
- GI events were uncommon (diarrhoea 10%, nausea 8%, vomiting 4%) [2].
- Least-squares mean weight reduction at week 12 ranged from 2.6% to 11.3% across cohorts [2].

• Phase 2 (Lancet; 263 adults with obesity or overweight without type 2 diabetes, 48 weeks; 78% female).

- Mean body-weight change across the eloralintide arms ranged from about −9% to −20%, compared with −0.4% on placebo (efficacy estimand) [3].
- Nausea and fatigue were the most common adverse events and were much more frequent in some arms: nausea up to 64% versus 14% on placebo, and fatigue up to 46% versus 12% [3].
- So the low gastrointestinal rates seen in Phase 1 did not carry over unchanged to longer treatment in every arm [2][3].

• Cardiometabolic signals. A review of the early studies reports reductions in pulse rate, blood pressure, inflammatory markers and lipids, along with preferential fat-mass loss. It notes that the fall in pulse rate contrasts with the heart-rate increase seen with GLP-1 receptor agonists [4]. The same review states that no amylin agonist, eloralintide included, has had a dedicated cardiovascular outcomes trial [4].

Evidence quality

• The human evidence is early-phase. It consists of two Phase 1 studies and one 48-week Phase 2 trial [1][2][3]. The registered Phase 3 studies are still recruiting [11][12][13]. One review describes the current evidence as coming from preclinical, Phase 1 and Phase 2 studies with relatively small samples and short durations [4].
• Almost all primary data come from the manufacturer (Eli Lilly–sponsored or Lilly-authored) [1][3][9]. No independent replication was found.
• The tolerability claims need context. The lower taste avoidance compared with cagrilintide is a rat finding [1]. In the human Phase 2 trial, nausea and fatigue were the most common adverse events, and their rates varied widely between arms [3]. No head-to-head human trial against another amylin agent was found.
• The Phase 2 population was 78% female and 78% White and excluded type 2 diabetes [3], which limits generalisation.

Research context

Phase 3 studies are recruiting, according to their registry entries:

• in obesity or overweight without type 2 diabetes [11]
• in obesity or overweight with type 2 diabetes [12]
• in people with persistent obesity on stable background incretin therapy [13]

A recruiting Phase 2 study is testing eloralintide and macupatide, alone or combined, in obesity or overweight with type 2 diabetes [14]. Recruiting Phase 3 studies also cover obstructive sleep apnea [15] and knee osteoarthritis pain [16]. Reviews place eloralintide among the long-acting amylin agents (cagrilintide, petrelintide and others) being studied both alone and in combination with incretin-based drugs [5][6]. It is investigational and not approved.

Storage and handling

Research-grade material is a lyophilized powder. Keep sealed vials cold, dry and away from light, per the batch COA or label. No eloralintide-specific stability data were found in the indexed sources.

Quality and COA considerations

At about 4.5 kDa [7], eloralintide is a large, modified peptide. A batch-specific COA should confirm identity by mass spectrometry and purity by HPLC. Because the catalog label "Amylin Agonist" is generic, check that the COA names eloralintide specifically. Other long-acting amylin analogues, such as cagrilintide, are different molecules with different receptor profiles [5]. Fill amounts in vendor listings are catalog facts only.

Key references

1. Briere et al., Mol Metab 2025 — discovery to clinical proof of concept — https://pubmed.ncbi.nlm.nih.gov/41109426/
2. Bhattachar et al., Diabetes Obes Metab 2026 — Phase 1 MAD — https://pubmed.ncbi.nlm.nih.gov/41559929/
3. Billings et al., Lancet 2025 — 48-week Phase 2 RCT — https://pubmed.ncbi.nlm.nih.gov/41207310/
4. Sigalov & Frishman, Cardiol Rev 2026 — cardiovascular implications (review) — https://pubmed.ncbi.nlm.nih.gov/42745233/
5. Fischer & Borner, Pharmacol Res 2026 — amylin pharmacotherapy and tolerability (review) — https://pubmed.ncbi.nlm.nih.gov/42586227/
6. Alhazmi & le Roux, Diabetes Obes Metab 2026 — amylin analogs (review) — https://pubmed.ncbi.nlm.nih.gov/42452898/
7. PubChem CID 175663130 — Eloralintide — https://pubchem.ncbi.nlm.nih.gov/compound/175663130
8. ChEMBL CHEMBL6068462 — Eloralintide — https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL6068462
9. Briere et al., ADA abstract 3082-LB — eloralintide + tirzepatide in DIO rats — https://www.semanticscholar.org/paper/72bed0c5b0ba7ae26fc01d6b531400882147479a
10. Zhao et al., ADA abstract 1664-P — amylin agonists vs eloralintide — https://www.semanticscholar.org/paper/0ccc4e341c5607dc518aa6cd136f4ce52c2ac7f6
11. NCT07321886 — Phase 3, without T2D — https://clinicaltrials.gov/study/NCT07321886
12. NCT07282600 — Phase 3, with T2D — https://clinicaltrials.gov/study/NCT07282600
13. NCT07392190 — Phase 3, on background incretin — https://clinicaltrials.gov/study/NCT07392190
14. ClinicalTrials.gov NCT07215559 — Phase 2, macupatide and eloralintide — https://clinicaltrials.gov/study/NCT07215559
15. ClinicalTrials.gov NCT07369011 — Obstructive sleep apnea — https://clinicaltrials.gov/study/NCT07369011
16. ClinicalTrials.gov NCT07353931 — Osteoarthritis knee pain — https://clinicaltrials.gov/study/NCT07353931

Research-use note: Educational summary of published research. Eloralintide is investigational and not approved; this is research context only, not medical advice, and contains no usage guidance.