How does eloralintide differ from semaglutide and tirzepatide?

Eloralintide works through the amylin receptor, not GLP-1 or GIP receptors. Amylin is a different satiety hormone co-released with insulin. Because it uses a separate pathway, eloralintide could potentially be combined with GLP-1 drugs for additive effects. Its side effect profile also differs — fatigue is more prominent than nausea.

How does eloralintide compare to pramlintide (Symlin)?

Pramlintide is an older amylin analog that requires multiple daily injections and activates both amylin and calcitonin receptors, contributing to nausea. Eloralintide is selective for the amylin receptor, has a ~2-week half-life enabling once-weekly dosing, and showed notably better tolerability in trials.

When will eloralintide be available?

Phase 3 enrollment began in late 2025. A Phase 2 combination study with tirzepatide is also underway. If Phase 3 is successful, the earliest FDA approval would likely be 2028-2029. It is not yet available outside of clinical trials.

Eloralintide

Eli Lilly's once-weekly selective amylin receptor agonist. Phase 2 trials showed up to 20% weight loss at 48 weeks with favorable tolerability. Phase 3 enrollment began late 2025.

EmergingLimited Data

What is Eloralintide?

Eloralintide (LY3841136) is a once-weekly, selective amylin receptor agonist developed by Eli Lilly. Amylin is a hormone co-secreted with insulin from pancreatic beta cells that promotes satiety and slows gastric emptying — similar to GLP-1 but through a distinct receptor pathway. Eloralintide's selectivity for the amylin receptor (rather than also activating calcitonin receptors) and its long half-life of approximately two weeks contribute to improved tolerability compared to older amylin analogs like pramlintide. In Phase 2 trials published in The Lancet, eloralintide achieved up to 20% body weight loss at 48 weeks — rivaling tirzepatide — with a side effect profile notable for fatigue rather than the severe nausea typical of GLP-1 drugs. Lilly is also studying eloralintide in combination with tirzepatide, which could push weight loss beyond what either achieves alone.

Why People Talk About It

Weight loss rivaling GLP-1/GIP dual agonists (up to 20%)

Emerging

Novel mechanism distinct from GLP-1 pathway

Moderate

Potential combination with tirzepatide for enhanced efficacy

Limited

Cardiometabolic risk factor improvement

Emerging

How It Works

Eloralintide mimics amylin, a natural hormone your pancreas releases alongside insulin after meals. Amylin tells your brain you're full and slows down stomach emptying. As a selective amylin receptor agonist, eloralintide activates this satiety signal without triggering related calcitonin receptors — which may explain why it's better tolerated than older amylin drugs.

Common Questions

Safety Information

Important Safety Notes

Common Side Effects

Nausea (11-64% depending on dose; lower with gradual escalation)Fatigue (up to 46% at higher doses)Decreased appetiteHeadache

Cautions

• Not yet FDA-approved — investigational drug
• Nausea and fatigue are dose-dependent and more common at higher doses
• Phase 1 found low GI side effects overall, but Phase 2 showed higher nausea at 6 mg
• Slower dose escalation significantly improved tolerability

What We Don't Know

Long-term safety beyond 48 weeks has not been studied. Cardiovascular outcomes data is pending. The combination with tirzepatide is still in Phase 2, so the safety profile of dual therapy is undefined. Effects on bone density, pancreatic health, and long-term metabolic outcomes are unknown.

Published Research

5 studies

Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators.

ReviewPMID: 41948476

Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes.

ReviewPMID: 41747885

Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept.

Clinical TrialPMID: 41559929

Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.

263 patients, 48 weeks, up to 20% weight loss

Randomized Controlled TrialPMID: 41207310

Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.

ReviewPMID: 41109426

Mechanism of Action

Eloralintide is a selective agonist of the amylin receptor (AMY1, AMY2, AMY3), which comprises the calcitonin receptor (CTR) complexed with receptor activity-modifying proteins (RAMPs). Unlike pramlintide, eloralintide demonstrates selectivity for amylin receptors over calcitonin receptors, which may contribute to its improved tolerability profile. Amylin receptors in the area postrema and nucleus tractus solitarius mediate satiety signaling, slowed gastric emptying, and suppressed postprandial glucagon secretion. Eloralintide's engineered long half-life (~2 weeks) enables once-weekly subcutaneous dosing. Phase 2 data (263 participants, 48 weeks) showed dose-dependent weight loss: -9% (1 mg), -12% (3 mg), -18% (6 mg), and -20% (9 mg) vs -0.4% placebo, with improvements in waist circumference, blood pressure, lipid profiles, glycemic control, and inflammatory markers. Phase 1 (100 participants, 12 weeks) confirmed dose-proportional pharmacokinetics with 2.6-11.3% weight loss.

Evidence Snapshot

Overall Confidence55%

Human Clinical Evidence

Moderate and growing. Phase 2 RCT published in The Lancet (263 participants, 48 weeks, 46 US sites): dose-dependent weight loss from 9% to 20% vs 0.4% placebo, with cardiometabolic improvements across all doses. Phase 1 (100 participants, 12 weeks) published in Diabetes, Obesity and Metabolism confirmed dose-proportional PK and 2.6-11.3% weight loss with good tolerability. Phase 3 enrollment began late 2025. Phase 2 combination study with tirzepatide is underway.

Animal / Preclinical

Supportive. Discovery-to-clinical-POC paper (PMID: 41109426) describes the preclinical rationale and optimization. Amylin biology is well-established from decades of pramlintide research.

Mechanistic Rationale

Strong. Amylin receptor signaling for satiety and metabolic regulation is well-validated by pramlintide's FDA approval and extensive amylin biology research. Eloralintide's innovation is receptor selectivity and extended half-life, not a novel pathway.

Forms & Administration

Eloralintide is administered as a once-weekly subcutaneous injection. Phase 2 tested doses from 1 mg to 9 mg with various escalation schedules. Slower dose escalation (3 mg → 9 mg) improved tolerability compared to starting at higher doses. It is currently only available through clinical trials.

Use Cases & Evidence Levels

Weight loss rivaling GLP-1/GIP dual agonists (up to 20%)

Emerging50%

Novel mechanism distinct from GLP-1 pathway

Moderate70%

Potential combination with tirzepatide for enhanced efficacy

Limited15%

Cardiometabolic risk factor improvement

Emerging50%

Safety Profile

Safety Information

Common Side Effects

Nausea (11-64% depending on dose; lower with gradual escalation)Fatigue (up to 46% at higher doses)Decreased appetiteHeadache

Cautions

• Not yet FDA-approved — investigational drug
• Nausea and fatigue are dose-dependent and more common at higher doses
• Phase 1 found low GI side effects overall, but Phase 2 showed higher nausea at 6 mg
• Slower dose escalation significantly improved tolerability

What We Don't Know

Published Research

5 studies

Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators.

ReviewPMID: 41948476

Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes.

ReviewPMID: 41747885

Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept.

Clinical TrialPMID: 41559929

Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.

263 patients, 48 weeks, up to 20% weight loss

Randomized Controlled TrialPMID: 41207310

Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.

ReviewPMID: 41109426

Related Peptides

Pramlintide

Strong

An FDA-approved synthetic analogue of amylin used alongside insulin for diabetes, also studied for weight management.

Tirzepatide

StrongBeginner

A dual GIP/GLP-1 receptor agonist FDA-approved for diabetes and weight management, producing the largest weight loss seen in clinical trials.

Semaglutide

StrongBeginner

A GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management, one of the most widely prescribed peptide drugs.

Cagrilintide

Emerging

A long-acting amylin analogue being developed in combination with semaglutide (CagriSema) for enhanced weight loss.

Retatrutide

Emerging

An investigational triple agonist (GIP/GLP-1/glucagon) from Eli Lilly. Not FDA-approved. Phase III TRIUMPH-4 results showed 23.7% weight loss — the most of any obesity drug in development.

Orforglipron

Moderate

Foundayo (orforglipron) is Eli Lilly's oral small-molecule GLP-1 receptor agonist. Phase 3 trials show up to 11.2% weight loss via daily pill — no injections required. Regulatory submissions expected 2026.

Quick Facts

Class: Amylin Receptor Agonist
Evidence: Emerging
Safety: Limited Data
Updated: Apr 2026
Citations: 5PubMed

Also known as

LY3841136LY-3841136

Evidence Score

Overall Confidence55%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.