Eloralintide vs Retatrutide (2026): Selective Amylin Agonist vs Triple Agonist in Lilly's Obesity Pipeline
Eloralintide vs retatrutide: up to 20% weight loss at 48 weeks for the amylin agonist vs 28.3% at 80 weeks for the triple agonist. See how the data compare.
Research reference only. The information in this article is a summary of peer-reviewed scientific literature. It does not constitute medical advice and is not intended to guide human use. See our full disclaimer.
Eloralintide vs retatrutide is a comparison of two once-weekly injectable peptides from the same developer that reduce body weight through different receptor systems: eloralintide is a selective amylin receptor agonist, while retatrutide is a triple agonist of the GIP, GLP-1 and glucagon receptors. This page summarizes the published trial data for each compound, explains why the two programs run in parallel, and flags where figures cannot be compared directly.
Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.
Quick Answer: In its 48-week Phase 2 trial, eloralintide reported mean body weight reductions of 9% to 20% across dose arms (PMID 41207310), while retatrutide reported 28.3% at 80 weeks at 12 mg in Phase 3 TRIUMPH-1. The compounds act on different receptors and were studied in separate trials, so the figures are descriptive only.
TL;DR:
- Eloralintide targets the amylin receptor only; retatrutide targets GIPR, GLP-1R and GCGR in one molecule
- Eloralintide: Phase 2 Lancet data (263 adults, 48 weeks), now in a multi-trial Phase 3 program
- Retatrutide: Phase 2 NEJM data (338 adults, 48 weeks) and Phase 3 TRIUMPH readouts
- Both are investigational, and no head-to-head trial exists
- Eloralintide has also been studied in combination with tirzepatide (EloraTZP), which links the two pipelines
| Parameter | Eloralintide | Retatrutide |
|---|---|---|
| Target | Amylin receptor agonist | GIPR / GLP-1R / GCGR triple agonist |
| Developer | Eli Lilly (LY3841136) | Eli Lilly (LY3437943) |
| Most advanced stage | Phase 3 program (obesity, T2D, sleep apnea, add-on) | Phase 3 (TRIUMPH program) with readouts reported |
| Lead evidence | Phase 2: -9% to -20% at 48 weeks vs -0.4% placebo | Phase 2: -24.2% at 48 weeks (12 mg); TRIUMPH-1: -28.3% at 80 weeks |
| Dosing interval | Once weekly, subcutaneous | Once weekly, subcutaneous |
| Regulatory status | Investigational | Investigational |
Eloralintide: mechanism and evidence base
Eloralintide is a selective amylin receptor agonist peptide. Amylin is co-secreted with insulin from pancreatic beta cells and signals satiety, and eloralintide mimics that signal without engaging GLP-1 or GIP receptors. Because it acts independently of the incretin pathway, it has been studied both as a monotherapy and as a candidate to layer onto incretin-based regimens.
The Phase 2 trial published in The Lancet in December 2025 (PMID 41207310; NCT06230523) randomised 263 adults with obesity or overweight and at least one weight-related comorbidity, without type 2 diabetes, across six eloralintide dose and titration arms or placebo for 48 weeks. Mean body weight reduction ranged from 9% at 1 mg to 20% at 9 mg and 6-9 mg, versus 0.4% with placebo, without a clear plateau at the higher doses. The most common adverse events were nausea and fatigue, generally dose-dependent.
The Phase 3 program includes studies in type 2 diabetes (NCT07282600), obstructive sleep apnea with obesity (NCT07369011), combination with the GIP agonist macupatide (NCT07215559), and add-on to an existing weekly incretin (NCT07392190). For a longer look at the amylin class, see eloralintide vs cagrilintide.
Retatrutide: mechanism and evidence base
Retatrutide is a single peptide that activates the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor and the glucagon receptor. In the published framing, GLP-1R and GIPR signalling are associated with appetite suppression and insulin secretion, while glucagon receptor signalling is associated with increased energy expenditure and hepatic fat oxidation.
A 2026 Molecular Metabolism study (PMID 41997446) examined this in rodents. Retatrutide normalized body weight in obese GLP-1R knock-out mice, and a GIPR:GCGR co-agonist lacking GLP-1 activity reduced excess body weight in diet-induced obese mice to a similar degree. This is preclinical mechanism context and does not predict human outcomes.
In humans, the Phase 2 obesity trial in the New England Journal of Medicine (PMID 37366315) randomised 338 adults to retatrutide 1 mg to 12 mg or placebo. At 48 weeks the 12 mg group reported -24.2% mean body weight change versus -2.1% for placebo. In Phase 3 TRIUMPH-1 (NCT05929066), 2,339 adults were enrolled and the sponsor reported -28.3% at 80 weeks for the 12 mg arm under the efficacy estimand, versus -2.2% for placebo. Details are in the TRIUMPH-1 results summary.
Side-by-side: amylin-only vs triple agonism
The two compounds represent different pharmacological strategies. Retatrutide combines three metabolic receptor signals in one molecule, while eloralintide isolates a single satiety axis that is separate from the incretin system.
| Comparison point | Eloralintide | Retatrutide 12 mg |
|---|---|---|
| Key trial | Phase 2, Lancet (48 weeks) | Phase 2 NEJM (48 weeks); TRIUMPH-1 (80 weeks) |
| Mean weight change | -9% to -20% (dose range) | -24.2% (Phase 2); -28.3% (TRIUMPH-1, efficacy estimand) |
| Placebo | -0.4% | -2.1% (Phase 2); -2.2% (TRIUMPH-1) |
| Receptor systems | Amylin | Incretin plus glucagon |
| Population | Obesity/overweight, no type 2 diabetes | Obesity/overweight, TRIUMPH-1 without diabetes |
| Common adverse events | Nausea, fatigue | Gastrointestinal events (dose-dependent) |
At 48 weeks the two Phase 2 trials reported different magnitudes (up to 20% versus 24.2%), but dose ranges, titration schedules and populations differ. These columns should not be ranked against each other.
Why one developer runs both programs
A single sponsor developing an amylin agonist and a triple incretin agonist reflects an interest in complementary mechanisms rather than direct competition. The EloraTZP Phase 2b trial (NCT06603571; reported at EASD in September 2026) studied eloralintide with tirzepatide in 367 adults with obesity or overweight and type 2 diabetes. At 48 weeks, the combination reached up to 23.3% weight loss versus 14.8% with tirzepatide 15 mg alone, with discontinuation due to adverse events of 10.8% to 27.0% in combination arms (efficacy estimand; see the EloraTZP summary). That data point shows how an amylin agonist is being tested as an add-on to an incretin, which is a different research question from the triple-agonist approach.
Differential research applications
Researchers studying glucagon-mediated energy expenditure and hepatic effects have used retatrutide for triple-receptor questions. Researchers studying amylin pharmacology have used eloralintide to test whether a distinct satiety axis adds to or substitutes for incretin signalling. The trial tracker lists registered studies for both compounds, and the half-life chart allows dosing intervals to be viewed together.
Regulatory status
Both compounds are investigational. Eloralintide has multiple Phase 3 trials recruiting or ongoing, and no New Drug Application had been reported as of this writing. Retatrutide has reported Phase 3 readouts, and the sponsor has stated it plans a Biologics License Application. Neither is approved by the FDA or EMA, and neither is eligible for 503A compounding as an investigational biologic peptide.
Cited studies
- PMID 41207310, "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, 2025). https://doi.org/10.1016/S0140-6736(25)02155-5
- PMID 37366315, "Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial" (New England Journal of Medicine, 2023). https://doi.org/10.1056/NEJMoa2301972
- PMID 41997446, "GIPR:GCGR co-agonism restores normal weight in obese rodents." (Molecular Metabolism, 2026). https://doi.org/10.1016/j.molmet.2026.102365
Frequently asked questions
Q: What is the difference between eloralintide and retatrutide?
A: Eloralintide is a selective amylin receptor agonist, while retatrutide is a triple agonist of the GIP, GLP-1 and glucagon receptors. Both are once-weekly injectables from the same developer, but they act on different receptor systems.
Q: Retatrutide vs eloralintide: which showed more weight loss in trials?
A: Retatrutide 12 mg reported 24.2% at 48 weeks in Phase 2 and 28.3% at 80 weeks in TRIUMPH-1, while eloralintide reported up to 20% at 48 weeks in Phase 2. The trials differ in design, dose and duration, and no head-to-head study exists.
Q: Is eloralintide a GLP-1 agonist?
A: No. Eloralintide acts on the amylin receptor and does not engage GLP-1 or GIP receptors, which is why it has been studied as an add-on to incretin-based regimens.
Q: Why does one company develop both eloralintide and retatrutide?
A: The mechanisms are complementary, so the programs address different research questions. The EloraTZP trial, which paired eloralintide with tirzepatide, illustrates the add-on approach.
Q: Are eloralintide and retatrutide approved?
A: Neither is approved by the FDA or EMA. Both remain investigational, with eloralintide in Phase 3 trials and retatrutide having reported Phase 3 readouts.
See also:
- Eloralintide vs cagrilintide: compares eloralintide with an established amylin analogue
- Retatrutide vs tirzepatide: triple versus dual incretin agonism
- EloraTZP Phase 2 results: the eloralintide plus tirzepatide combination trial
For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.