reptides / eloralintide

eloralintide

Eloralintide has one published human efficacy trial. The phase 2 result reached about 20% average weight loss in selected arms, but nausea varied sharply by regimen and the phase 3 program has no efficacy results yet.

Selective long-acting AMY1 amylin receptor agonist

  • Once-weekly investigational peptide
  • Designed to favor the AMY1 receptor
  • Phase 3 ENLIGHTEN trials are ongoing
Is it approved? Which arm reached 20%? Did escalation fix nausea? Does AMY1 selectivity reduce side effects? What must phase 3 answer?

Is eloralintide approved, and what human results are available?

Eloralintide remains investigational. One peer-reviewed 263-person phase 2 efficacy trial has reported 48-week weight results; registered phase 3 ENLIGHTEN studies have not yet supplied efficacy outcomes.

The phase 3 registrations provide protocols, planned endpoints, and completion dates. They do not yet provide results.

FDA records · eloralintide status

Regulatory database record set

FDA Drugs@FDA and openFDA records

The cited U.S. approval records contain no exact-name eloralintide or LY3841136 entry.

Participants / model
United States drug approvals
Treatment
Eloralintide and LY3841136
Study design
Exact-name and development-code U.S. approval coverage
Read the original source
Eloralintide phase 2 · arm-level efficacy and nausea

Randomized trial

Wharton et al., The Lancet, 2025

In 263 U.S. adults, efficacy-estimand mean weight change ranged from -9% to -20% across six regimens versus -0.4% with placebo; nausea and fatigue varied substantially across small arms.

Participants / model
Adults with obesity or overweight plus a comorbidity, without type 2 diabetes
Treatment
Weekly eloralintide fixed or escalation regimens or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind, placebo-controlled phase 2 trial
Funding
Eli Lilly

Small individual arms and an efficacy estimand limit certainty about real-world treatment persistence.

Read the original source

Which eloralintide arms reached about 20% weight loss?

Under the efficacy estimand at week 48, mean change was -20% in the fixed 9 mg arm and -20% in the 6-to-9 mg escalation arm, versus -0.4% with placebo. Other arms ranged from -9% to -18%, except the 3-to-9 mg escalation arm at -16%.

Eloralintide phase 2 week-48 efficacy-estimand weight change
RegimenMean change
1 mg-9%
3 mg-12%
6 mg-18%
9 mg-20%
6 to 9 mg-20%
3 to 9 mg-16%
Placebo-0.4%
Eloralintide phase 2 · arm-level efficacy and nausea

Randomized trial

Wharton et al., The Lancet, 2025

In 263 U.S. adults, efficacy-estimand mean weight change ranged from -9% to -20% across six regimens versus -0.4% with placebo; nausea and fatigue varied substantially across small arms.

Participants / model
Adults with obesity or overweight plus a comorbidity, without type 2 diabetes
Treatment
Weekly eloralintide fixed or escalation regimens or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind, placebo-controlled phase 2 trial
Funding
Eli Lilly

Small individual arms and an efficacy estimand limit certainty about real-world treatment persistence.

Read the original source

Why did nausea differ so much across arms?

Nausea ranged from 11% to 64% across active arms versus 14% with placebo. Fatigue ranged from 0% to 46% versus 12% with placebo. Neither pattern followed a simple dose order: fixed 6 mg had 64% nausea, fixed 9 mg had 33%, 6-to-9 mg escalation had 54%, and 3-to-9 mg escalation had 25%.

Each active arm enrolled only 24 to 54 participants. The abstract does not report regimen-specific discontinuation, so it cannot show whether escalation reliably prevented treatment-limiting symptoms.

Eloralintide phase 2 · arm-level efficacy and nausea

Randomized trial

Wharton et al., The Lancet, 2025

In 263 U.S. adults, efficacy-estimand mean weight change ranged from -9% to -20% across six regimens versus -0.4% with placebo; nausea and fatigue varied substantially across small arms.

Participants / model
Adults with obesity or overweight plus a comorbidity, without type 2 diabetes
Treatment
Weekly eloralintide fixed or escalation regimens or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind, placebo-controlled phase 2 trial
Funding
Eli Lilly

Small individual arms and an efficacy estimand limit certainty about real-world treatment persistence.

Read the original source

Does AMY1 receptor selectivity mean fewer side effects?

No. Preclinical receptor assays support the selective AMY1 design, but the human phase 2 trial still recorded frequent nausea and fatigue in several arms. Receptor assays cannot establish a lower clinical side-effect rate.

Eloralintide · AMY1 selectivity

Preclinical study

Lilly investigators, 2025

Receptor and animal experiments characterize eloralintide as a long-acting agonist with preference for AMY1.

Participants / model
Receptor systems and animal models
Treatment
Eloralintide
Follow-up
Preclinical experiments
Study design
In vitro pharmacology and animal studies
Funding
Eli Lilly

Selectivity in assays does not establish superior human efficacy or tolerability.

Read the original source
Eloralintide phase 2 · arm-level efficacy and nausea

Randomized trial

Wharton et al., The Lancet, 2025

In 263 U.S. adults, efficacy-estimand mean weight change ranged from -9% to -20% across six regimens versus -0.4% with placebo; nausea and fatigue varied substantially across small arms.

Participants / model
Adults with obesity or overweight plus a comorbidity, without type 2 diabetes
Treatment
Weekly eloralintide fixed or escalation regimens or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind, placebo-controlled phase 2 trial
Funding
Eli Lilly

Small individual arms and an efficacy estimand limit certainty about real-world treatment persistence.

Read the original source

What are the ENLIGHTEN trials meant to add?

The ENLIGHTEN program registers phase 3 studies in obesity and obesity-related conditions, including obstructive sleep apnea. Their role is to test efficacy and safety in larger, defined populations. Registered endpoints and future completion dates are not results.

Any claim that eloralintide outperforms another obesity medicine or preserves weight after stopping remains open until an appropriate trial reports.

ENLIGHTEN program · phase 3 registry

Clinical trial registry

ClinicalTrials.gov, NCT07369011

The registry record describes a phase 3 eloralintide trial in people with obstructive sleep apnea and obesity or overweight and posts no efficacy result.

Participants / model
Adults with obstructive sleep apnea and obesity or overweight
Treatment
Eloralintide or comparator per protocol
Follow-up
Phase 3 follow-up
Study design
Randomized phase 3 registry record

This record represents one ENLIGHTEN trial and does not establish the status of the other four phase 3 studies.

Read the original source

Studies and sources

FDA records · eloralintide status

Regulatory database record set

FDA Drugs@FDA and openFDA records

The cited U.S. approval records contain no exact-name eloralintide or LY3841136 entry.

Participants / model
United States drug approvals
Treatment
Eloralintide and LY3841136
Study design
Exact-name and development-code U.S. approval coverage
Read the original source
Eloralintide phase 2 · arm-level efficacy and nausea

Randomized trial

Wharton et al., The Lancet, 2025

In 263 U.S. adults, efficacy-estimand mean weight change ranged from -9% to -20% across six regimens versus -0.4% with placebo; nausea and fatigue varied substantially across small arms.

Participants / model
Adults with obesity or overweight plus a comorbidity, without type 2 diabetes
Treatment
Weekly eloralintide fixed or escalation regimens or placebo
Follow-up
48 weeks
Study design
Randomized, double-blind, placebo-controlled phase 2 trial
Funding
Eli Lilly

Small individual arms and an efficacy estimand limit certainty about real-world treatment persistence.

Read the original source
Eloralintide · AMY1 selectivity

Preclinical study

Lilly investigators, 2025

Receptor and animal experiments characterize eloralintide as a long-acting agonist with preference for AMY1.

Participants / model
Receptor systems and animal models
Treatment
Eloralintide
Follow-up
Preclinical experiments
Study design
In vitro pharmacology and animal studies
Funding
Eli Lilly

Selectivity in assays does not establish superior human efficacy or tolerability.

Read the original source
ENLIGHTEN program · phase 3 registry

Clinical trial registry

ClinicalTrials.gov, NCT07369011

The registry record describes a phase 3 eloralintide trial in people with obstructive sleep apnea and obesity or overweight and posts no efficacy result.

Participants / model
Adults with obstructive sleep apnea and obesity or overweight
Treatment
Eloralintide or comparator per protocol
Follow-up
Phase 3 follow-up
Study design
Randomized phase 3 registry record

This record represents one ENLIGHTEN trial and does not establish the status of the other four phase 3 studies.

Read the original source

Why is eloralintide in B tier?

The B tier reflects a large phase 2 weight-loss signal and an active phase 3 program. Eloralintide remains unapproved, with no established cardiovascular benefit, post-treatment durability, or lower nausea and fatigue rates than other amylin drugs.

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