Eloralintide: what it is, how it works and what studies have found

Eloralintide is a long-acting amylin analogue built to favour one amylin receptor subtype. Its evidence base is small but peer reviewed: one discovery and translational paper, one multiple-ascending-dose phase 1 trial and one 48-week phase 2 trial, with phase 3 now under way. Combination data with tirzepatide exist only as conference presentations. This overview reports what each source shows and labels the evidence level of each finding. It reports published research and is not medical guidance.

What is eloralintide?

Eloralintide (code LY3841136) is a synthetic analogue of human amylin, the 37-amino-acid peptide hormone co-secreted with insulin by pancreatic beta cells [1]. Its sequence changes are intended to allow once-weekly subcutaneous administration, reduce immunogenicity risk, improve developability and give amylin receptor selectivity [1]. KEGG lists it under the USAN eloralintide, targeting the calcitonin receptor (CALCR) and calcitonin receptor-like receptor (CALCRL) families [2].

Amylin receptors are heterodimers of the calcitonin receptor with one of three receptor activity-modifying proteins (RAMP1 to RAMP3), giving AMY1R, AMY2R and AMY3R [3]. Most long-acting amylin analogues in development also activate the calcitonin receptor alone; eloralintide was designed to prefer AMY1R [1].

Eloralintide structure, sequence and molecular weight

The developers describe eloralintide as a C-terminally amidated linear peptide of 37 amino acids in the main chain, all L-configuration, with three non-coded residues at positions 11, 15 and 22 [1]. The native amylin disulfide is replaced by a methylene thioacetal bridge between Cys2 and Cys7 for chemical stability, and Lys26 carries a side chain of two gamma-glutamate residues and a saturated linear 20-carbon diacid, which binds albumin and extends half-life [1].

Property	Eloralintide
Name	Eloralintide (USAN) [2]
Development code	LY3841136 [1]
CAS number	2883634-40-8 [4]
Molecular formula	C201H319N49O65S2 [2][4]
Average molecular weight	4526.11 g/mol (KEGG); 4526 (PubChem) [2][4]
Main-chain length	37 amino acids, C-terminal amide [1]
Sequence (KEGG one-letter code)	XCNTATCATGXLAEFLVRSSNNFGPKLPPTEVGSNTY [2]
Non-coded residues	Positions 11, 15 and 22 [1]
Bridge	Methylene thioacetal between Cys2 and Cys7 (replaces disulfide) [1]
Side chain	Lys26: gamma-Glu-gamma-Glu-C20 diacid [1]
Receptor preference	AMY1R over CTR and AMY3R [1]

The KEGG one-letter string marks some residues as X and does not show the thioacetal bridge or the Lys26 side chain [2], so identity should be confirmed against the full structure in the developers’ paper and by intact mass rather than from the one-letter string alone [1].

Eloralintide mechanism of action

Receptor selectivity (in vitro). In UMUC3 cells expressing single human receptors, eloralintide stimulated cAMP at AMY1R with an EC50 of 23.9 pM, about 12-fold more potent than at the calcitonin receptor (291.0 pM) and about 11-fold more potent than at AMY3R (253.8 pM); potency at AMY3R and CTR was similar [1]. Selectivity over CTR was maintained in the presence of albumin [1]. At rat receptors, both AMY1R and AMY3R were activated more potently than CTR [1]. Evidence level: in vitro.

Food intake and body weight (animal). In diet-induced obese rats, eloralintide reduced food intake and body weight dose-dependently, mainly through fat-mass loss [1]. In lean rats it produced significantly less conditioned taste avoidance, a rodent test used to assess aversive effects, than cagrilintide [1]. Pharmacokinetics in rats and monkeys showed higher exposure, longer half-life and flatter concentration-time curves than cagrilintide [1]. Evidence level: animal.

Gastric emptying (human). In the phase 1 multiple-dose trial, acetaminophen absorption tests showed a modest initial lowering of exposure after the first dose at higher doses, which returned to baseline with continued dosing; the authors suggest any effect on gastric emptying may be transient [5]. Evidence level: phase 1.

Eloralintide half-life and pharmacokinetics

In the single-ascending-dose phase 1 study in healthy participants, plasma concentrations declined monophasically after Tmax, with a terminal geometric mean half-life of 310 to 366 hours (12.9 to 15.3 days) across the dose range where it could be calculated reliably [1]. AUC was dose-proportional across the higher part of the dose range, while Cmax increased less than proportionally [1]. In the 12-week multiple-dose study, steady-state AUC and Cmax were dose-proportional, with dose-normalised geometric mean ratios of 1.1 and 1.0 [5]. For comparison, the same paper cites a cagrilintide half-life of 159 to 195 hours (6.6 to 8.1 days) [1].

Development history and timeline

Eloralintide was discovered and is developed by Eli Lilly and Company, which funded the published trials [1][6].

Date	Milestone	Ref
Mar 2022 to Jan 2024	Phase 1 multiple-ascending-dose study (100 participants, three US centres)	[5]
Feb 2024	Phase 2 trial (NCT06230523) starts	[6][7]
Aug 2025	Phase 2 completed	[6]
Oct 2025	Discovery and single-dose phase 1 data published	[1]
Nov 2025	48-week phase 2 results published in The Lancet	[6]
Dec 2025	ENLIGHTEN-2 (obesity with type 2 diabetes) starts	[8]
Feb 2026	ENLIGHTEN-1 (obesity without type 2 diabetes) starts	[9]
Jun 2026	Rat combination study with tirzepatide presented at ADA (conference abstract)	[10]
Sep 2026	Phase 2 EloraTZP data in type 2 diabetes presented at EASD (conference only)	[11]

Eloralintide clinical trials: key studies and findings

Study	Phase / design	Population	n	Duration	Primary endpoint	Main finding	Evidence status	Ref
NCT05295940	1, single ascending dose vs placebo	Healthy participants, mean BMI 27.5	48	Single dose; weight at week 4	Safety, tolerability	Half-life 12.9 to 15.3 days; week-4 weight -2.5% and -4.4% in two higher-dose cohorts vs +0.6%	Peer reviewed	[1]
Phase 1 MAD	1, five dose cohorts, no escalation, vs placebo	Obesity or overweight, mean BMI 32.6	100	12 weeks	Safety, PK, PD	LS mean weight reduction 2.6% to 11.3% across cohorts	Peer reviewed	[5]
NCT06230523	2, six regimens incl. two escalation schemes, vs placebo	Obesity or overweight with comorbidity, no type 2 diabetes	263	48 weeks	% weight change	-9% to -20% vs -0.4% (efficacy estimand)	Peer reviewed	[6]
EloraTZP phase 2	2, eloralintide alone or with tirzepatide, vs tirzepatide alone and placebo	Obesity or overweight with type 2 diabetes	367	48 weeks	Not stated in report	Highest-dose combination -23.3% vs -14.8% tirzepatide alone, -3% placebo	Conference presentation only	[11]

Phase 1 single-ascending-dose study

Forty-eight healthy participants (mean BMI 27.5 kg/m²) received single doses or placebo [1]. Nine participants in eloralintide cohorts reported 16 adverse events, 15 of them mild; two participants reported four gastrointestinal events, including one moderate vomiting event [1]. In two of the higher single-dose cohorts, mean body-weight change at week 4 was -2.5% and -4.4% versus +0.6% with placebo [1]. Evidence level: phase 1, small.

Phase 1 multiple-ascending-dose study

This 12-week trial randomised 100 participants with obesity or overweight (mean age 44 years, 29% female, mean BMI 32.6 kg/m²) at three US centres to five dose cohorts or placebo, starting each cohort directly at its target dose without escalation [5]. Least-squares mean body-weight reduction at week 12 ranged from 2.6% to 11.3% across dose groups [5]. Evidence level: phase 1, short duration.

Phase 2 trial (48 weeks)

The phase 2 trial enrolled 263 adults with a BMI of 30 kg/m² or more, or 27 kg/m² or more with a weight-related comorbidity, and without type 2 diabetes, at 46 US research centres between February 2024 and August 2025 [6]. Participants were randomised to four fixed-dose regimens, two dose-escalation regimens or placebo [6]. Baseline mean age was 49.0 years, mean weight 109.1 kg and mean BMI 39.1 kg/m²; 78% were female [6]. Mean body-weight change at week 48 (efficacy estimand) was -9%, -12%, -18% and -20% across the four fixed-dose arms and -20% and -16% in the two escalation arms, versus -0.4% with placebo [6]. Evidence level: phase 2, US only, predominantly female.

Conference-only data: eloralintide with tirzepatide

A phase 2 trial of eloralintide alone or combined with tirzepatide in 367 adults with obesity or overweight and type 2 diabetes was presented at the European Association for the Study of Diabetes meeting in September 2026 [11]. As reported, the highest-dose combination arm reached -23.3% body-weight change at 48 weeks (efficacy estimand) versus -14.8% with tirzepatide alone and -3% with placebo, and HbA1c fell by 2.2 to 2.9 percentage points across combination arms versus 0.3 with placebo [11]. These figures come from a conference presentation and a news report of it, not from a peer-reviewed publication, and should be treated as provisional. Evidence level: phase 2, conference only.

In diet-induced obese rats, a developer poster at the 2026 ADA meeting reported additive body-weight lowering over 4 weeks when eloralintide and tirzepatide were co-administered (-20%) compared with eloralintide (-10%) or tirzepatide (-9%) alone [10]. Evidence level: animal, conference abstract.

Phase 3 programme

ENLIGHTEN-1 (obesity or overweight without type 2 diabetes, 1,980 participants) and ENLIGHTEN-2 (obesity or overweight with type 2 diabetes, 1,035 participants) are recruiting [9][8]. AMPLIFY-1 (2,115 participants) will test the eloralintide-tirzepatide combination in obesity without type 2 diabetes [12].

Safety findings reported in eloralintide studies

• Phase 1 multiple-dose: most common adverse events were decreased appetite (19%), headache (12%), fatigue (11%) and COVID-19 (11%); gastrointestinal events were infrequent (diarrhoea 10%, nausea 8%, vomiting 4%); most events were mild; one serious adverse event was judged unrelated; no deaths [5].
• Phase 2 (48 weeks): nausea was the most common adverse event, ranging from 11% to 64% across eloralintide arms versus 14% with placebo, and fatigue from 0% to 46% versus 12% [6].
• Combination (conference only): nausea, fatigue and vomiting were more frequent in the highest-dose combination arm than with tirzepatide alone; 6.5% of participants had at least one serious adverse event [11].

Fatigue was reported more often in several eloralintide arms than with placebo (up to 46% versus 12%) [6]; the phase 3 ENLIGHTEN trials will give larger safety datasets [9].

Regulatory status of eloralintide by region

Region	Status (October 2026)	Ref
United States	Investigational; phase 3 (ENLIGHTEN)	[9]
European Union	Investigational; no EMA authorisation	[9]
United Kingdom	Investigational; no marketing authorisation identified	[9]
India	Investigational; no marketing authorisation identified	[9]
China	Investigational; no approval identified	[9]

No regulator has approved eloralintide, alone or in combination.

Eloralintide in laboratory research

• Receptor selectivity panels. The published approach used ligand-binding and cAMP assays in UMUC3 cells expressing human AMY1R, AMY3R or CTR, with rat amylin (selective) and salmon calcitonin (non-selective) as reference peptides, and repeated the assays with albumin present [1].
• Behavioural tolerability. Conditioned taste avoidance in lean rats was used to compare aversive effects with cagrilintide [1].
• Efficacy models. Diet-induced obese rats for food intake, body weight and body composition [1]; combination studies with tirzepatide in the same model [10].
• Analytical characterisation. Identity by LC-MS intact mass against 4526.11 g/mol and peptide mapping across the thioacetal-bridged N-terminal ring and the Lys26 side chain; purity by reversed-phase HPLC or UPLC [2].

Synthesis, purity and impurities

Eloralintide is produced by chemical synthesis, typically Fmoc solid-phase peptide synthesis (SPPS), with on-resin or post-assembly formation of the methylene thioacetal bridge and orthogonal protection of Lys26 for side-chain assembly. See SPPS versus LPPS.

Structure-linked impurity classes include deletion sequences, D-amino acid variants, uncyclised or mis-bridged species (free thiols or disulfide-bridged forms instead of the thioacetal), deamidation of the several Asn residues, incomplete or truncated side chains and aspartimide-related variants. Amylin-derived sequences tend to aggregate, so purity methods should be checked for loss of material on the column. See peptide API impurities and specifications.

Storage and stability of lyophilized eloralintide

Research eloralintide is supplied as a lyophilized (freeze-dried) powder. Typical laboratory practice is storage at -20 °C or below, protected from light and moisture, with vials equilibrated to room temperature before opening. The thioacetal bridge was introduced to improve chemical stability over the native disulfide [1], but solutions should still be prepared fresh and checked for clarity because amylin analogues can aggregate. See lyophilised peptide stability and storage.

Eloralintide versus related amylin peptides

Feature	Eloralintide	Cagrilintide	Amycretin
Type	Selective amylin analogue (AMY1R-preferring) [1]	Non-selective amylin analogue [1]	Unimolecular GLP-1 and amylin/calcitonin receptor agonist [3]
Reported half-life	12.9 to 15.3 days (phase 1) [1]	6.6 to 8.1 days (as cited by Briere et al.) [1]	Not reported in human abstracts; 29.3 hours in non-human primates (intravenous) [3]
Representative weight data	Up to -20% vs -0.4% at 48 weeks, phase 2 [6]	With semaglutide: -20.4% vs -3.0% at 68 weeks, phase 3 [13]	-24.3% vs -1.1% at 36 weeks, phase 1b/2a highest-dose part [14]
Most advanced phase	Phase 3 [9]	Phase 3 completed in combination [13]	Phase 3 (AMAZE, from 2026) [15]

A 2026 network meta-analysis placed high-dose eloralintide second for placebo-adjusted weight change among novel amylin-based therapies (mean difference -18.01%), after high-dose subcutaneous amycretin, while describing the evidence as sparse and of low certainty [16]. Cross-trial differences in duration, population and estimand make these comparisons indicative only. Amycretin is reviewed in amycretin: structure, mechanism and research findings.

How Winhycare Pharma supplies eloralintide

Winhycare Pharma supplies eloralintide as research-use-only material to research organisations and laboratories, at a purity of 99% or higher as stated in our product brochure, with a certificate of analysis covering HPLC purity and mass confirmation. Custom synthesis of eloralintide analogues and labelled variants is available. Product details are on the eloralintide research peptide page, and enquiries go through our research peptide contact form.

For laboratory research use only. Not for human or veterinary use.