retatrutide

updated September 11, 2026

What is retatrutide?

Retatrutide activates three receptors in laboratory systems, and its human trials show weight and liver-fat changes. Those data do not isolate how much of the clinical effect came from glucagon-receptor activity or prove a specific percentage increase in human energy expenditure.

In TRIUMPH-1, the 12 mg arm averaged 28.3% weight loss at week 80 under the efficacy estimand and 25.0% under the treatment-regimen estimand. Retatrutide remains investigational, and products sold outside Lilly trials may be fake, contaminated, or incorrectly dosed.

GIP, GLP-1, and glucagon receptor triple agonist

Once-weekly investigational peptide
Activates GIP, GLP-1, and glucagon receptors
No regulator has approved a retail retatrutide product

Is retatrutide approved, and what product was actually studied?

No. Lilly states that retatrutide is investigational and has not been approved by any regulator. Trial results apply to Lilly's controlled study drug, not products sold online under the same name.

A vial labeled retatrutide outside a trial has no regulator-confirmed identity, purity, or dose. That breaks the link between the clinical evidence and the purchased product.

Lilly status page · investigational product

Sponsor status page

Eli Lilly and Company, 2026.

Lilly states that retatrutide is not approved by any regulator and warns against products sold as retatrutide outside its trials.

Participants / model: General public
Treatment: No authorized treatment
Follow-up: Current status page
Study design: Sponsor statement

Sponsor information is primary for development status but is not independent evidence of efficacy.

Read the original source

Which retatrutide results are peer reviewed, and which are sponsor reported?

The 338-person, 48-week phase 2 obesity trial provides the peer-reviewed dose-ranging evidence. The 80-week TRIUMPH-1 result and selected 104-week extension figures come from Lilly’s May 2026 disclosure and the trial registry rather than a full peer-reviewed phase 3 paper.

The phase 2 paper reported dose-dependent weight loss and safety over 48 weeks. It cannot substitute for complete phase 3 reporting because the later trial enrolled a much larger population, ran longer, and used its own estimands.

Retatrutide phase 2 · obesity

Randomized trial

Jastreboff et al., New England Journal of Medicine, 2023

In 338 adults, retatrutide produced dose-dependent weight reduction over 48 weeks; gastrointestinal adverse events were the most common.

Participants / model: Adults with BMI at least 30, or at least 27 with a weight-related condition, without diabetes
Treatment: Weekly retatrutide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-blind phase 2 trial

The trial was not designed to isolate the contribution of each receptor.

Read the original source

TRIUMPH-1 · 80- and 104-week sponsor results

Sponsor phase 3 disclosure

Eli Lilly and Company, May 21, 2026

Reports week-80 efficacy and treatment-regimen estimates for 2,339 randomized participants, plus a selected 532-person extension and adverse-event tables.

Participants / model: Adults with obesity or overweight plus a comorbidity, without diabetes
Treatment: Weekly retatrutide 4, 9, or 12 mg or placebo; extension placebo participants switched to retatrutide
Follow-up: 80 weeks, with a selected 104-week extension
Study design: Randomized phase 3 trial with sponsor-reported extension

The 80-week efficacy and safety values and selected 104-week extension figures come from Lilly’s May 2026 disclosure rather than a full peer-reviewed phase 3 report.

Read the original source

TRIUMPH-1 · protocol and enrollment

Clinical trial registry

ClinicalTrials.gov, NCT05929066

Defines the randomized obesity population, interventions, outcomes, and trial status.

Participants / model: Adults with obesity or overweight plus a complication, without type 2 diabetes
Treatment: Retatrutide dose arms or placebo
Follow-up: Phase 3 follow-up
Study design: Randomized, parallel assignment

The registry reports trial design but not the sponsor’s outcome values.

Read the original source

What did TRIUMPH-1 report at 80 weeks, and what does the 104-week extension add?

Among 2,339 adults without diabetes, the 12 mg arm averaged 28.3% weight loss at week 80 under the efficacy estimand and 25.0% under the treatment-regimen estimand, versus 2.2% and 3.9% with placebo. The 104-week 30.3% figure came from a smaller extension subgroup of 532 people with baseline BMI at least 35 who completed week 80 and tolerated their assigned dose.

The two estimands answer different questions. The efficacy estimand estimates the effect if assigned treatment continued without rescue. The treatment-regimen estimand includes discontinuation, rescue, and dose changes.

The extension is informative about continued treatment among selected completers. It is not a fresh randomized estimate for all 2,339 original participants.

TRIUMPH-1 reported mean body-weight change
Time and analysis	Retatrutide 12 mg	Placebo condition
Week 80, efficacy estimand	-28.3%	-2.2%
Week 80, treatment-regimen estimand	-25.0%	-3.9%
Week 104 extension, efficacy estimand	-30.3%	-19.2% after placebo group switched to retatrutide

Week 104 used a selected extension cohort and no longer compared retatrutide with continued placebo.

TRIUMPH-1 · 80- and 104-week sponsor results

Sponsor phase 3 disclosure

Eli Lilly and Company, May 21, 2026

Reports week-80 efficacy and treatment-regimen estimates for 2,339 randomized participants, plus a selected 532-person extension and adverse-event tables.

Participants / model: Adults with obesity or overweight plus a comorbidity, without diabetes
Treatment: Weekly retatrutide 4, 9, or 12 mg or placebo; extension placebo participants switched to retatrutide
Follow-up: 80 weeks, with a selected 104-week extension
Study design: Randomized phase 3 trial with sponsor-reported extension

The 80-week efficacy and safety values and selected 104-week extension figures come from Lilly’s May 2026 disclosure rather than a full peer-reviewed phase 3 report.

Read the original source

TRIUMPH-1 · protocol and enrollment

Clinical trial registry

ClinicalTrials.gov, NCT05929066

Defines the randomized obesity population, interventions, outcomes, and trial status.

Participants / model: Adults with obesity or overweight plus a complication, without type 2 diabetes
Treatment: Retatrutide dose arms or placebo
Follow-up: Phase 3 follow-up
Study design: Randomized, parallel assignment

The registry reports trial design but not the sponsor’s outcome values.

Read the original source

Has retatrutide been directly compared with tirzepatide, semaglutide, or bariatric surgery?

No direct randomized comparison with those treatments is reported in the available TRIUMPH-1 material. Cross-trial rankings are unreliable because populations, follow-up, estimands, dose escalation, and handling of discontinuation differ.

TRIUMPH-1 did not compare retatrutide with surgery or another medicine.

TRIUMPH-1 · 80- and 104-week sponsor results

Sponsor phase 3 disclosure

Eli Lilly and Company, May 21, 2026

Reports week-80 efficacy and treatment-regimen estimates for 2,339 randomized participants, plus a selected 532-person extension and adverse-event tables.

Participants / model: Adults with obesity or overweight plus a comorbidity, without diabetes
Treatment: Weekly retatrutide 4, 9, or 12 mg or placebo; extension placebo participants switched to retatrutide
Follow-up: 80 weeks, with a selected 104-week extension
Study design: Randomized phase 3 trial with sponsor-reported extension

The 80-week efficacy and safety values and selected 104-week extension figures come from Lilly’s May 2026 disclosure rather than a full peer-reviewed phase 3 report.

Read the original source

What safety findings did TRIUMPH-1 report?

Gastrointestinal events were common and dose related. At 12 mg, the sponsor reported nausea in 42.4%, diarrhea in 32.0%, constipation in 26.1%, vomiting in 25.3%, dysesthesia in 12.5%, and adverse-event discontinuation in 11.3%; placebo values were 10.1%, 14.2%, 12.6%, 5.6%, 0.9%, and 4.9%. Those phase 3 safety figures come from the sponsor disclosure rather than a full peer-reviewed report.

Dysesthesia is an altered-sensation symptom, not a mechanism diagnosis. Sponsor tables establish incidence in this trial, not its cause or long-term course.

In the peer-reviewed phase 2 trial, heart rate rose in a dose-dependent pattern, peaked at week 24, and then declined. The abstract does not supply enough detail to treat that trajectory as clinically harmless or to predict an individual response.

TRIUMPH-1 · 80- and 104-week sponsor results

Sponsor phase 3 disclosure

Eli Lilly and Company, May 21, 2026

Reports week-80 efficacy and treatment-regimen estimates for 2,339 randomized participants, plus a selected 532-person extension and adverse-event tables.

Participants / model: Adults with obesity or overweight plus a comorbidity, without diabetes
Treatment: Weekly retatrutide 4, 9, or 12 mg or placebo; extension placebo participants switched to retatrutide
Follow-up: 80 weeks, with a selected 104-week extension
Study design: Randomized phase 3 trial with sponsor-reported extension

The 80-week efficacy and safety values and selected 104-week extension figures come from Lilly’s May 2026 disclosure rather than a full peer-reviewed phase 3 report.

Read the original source

Retatrutide phase 2 · obesity

Randomized trial

Jastreboff et al., New England Journal of Medicine, 2023

In 338 adults, retatrutide produced dose-dependent weight reduction over 48 weeks; gastrointestinal adverse events were the most common.

Participants / model: Adults with BMI at least 30, or at least 27 with a weight-related condition, without diabetes
Treatment: Weekly retatrutide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-blind phase 2 trial

The trial was not designed to isolate the contribution of each receptor.

Read the original source

What does the glucagon-receptor arm add?

Retatrutide activates three receptors in laboratory systems, and its human trials show weight and liver-fat changes. Those data do not isolate how much of the clinical effect came from glucagon-receptor activity or prove a specific percentage increase in human energy expenditure.

The receptor design is established. The exact contribution of each receptor in people remains a mechanistic interpretation because the obesity trials did not randomize participants to otherwise identical drugs with and without the glucagon arm.

Retatrutide phase 2 · obesity

Randomized trial

Jastreboff et al., New England Journal of Medicine, 2023

In 338 adults, retatrutide produced dose-dependent weight reduction over 48 weeks; gastrointestinal adverse events were the most common.

Participants / model: Adults with BMI at least 30, or at least 27 with a weight-related condition, without diabetes
Treatment: Weekly retatrutide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-blind phase 2 trial

The trial was not designed to isolate the contribution of each receptor.

Read the original source

Retatrutide · liver-fat substudy

Randomized substudy

Sanyal et al., Nature Medicine, 2024

A phase 2 substudy reported substantial liver-fat reduction, including normalization in many participants at higher doses.

Participants / model: Adults with obesity and MASLD in a retatrutide phase 2 substudy
Treatment: Weekly retatrutide or placebo
Follow-up: 24 and 48 weeks
Study design: Randomized substudy using MRI-derived liver fat

Liver-fat imaging does not isolate receptor contribution and is not the same as a biopsy-confirmed clinical outcome.

Read the original source

Studies and sources

Lilly status page · investigational product

Sponsor status page

Eli Lilly and Company, 2026.

Lilly states that retatrutide is not approved by any regulator and warns against products sold as retatrutide outside its trials.

Participants / model: General public
Treatment: No authorized treatment
Follow-up: Current status page
Study design: Sponsor statement

Sponsor information is primary for development status but is not independent evidence of efficacy.

Read the original source

TRIUMPH-1 · 80- and 104-week sponsor results

Sponsor phase 3 disclosure

Eli Lilly and Company, May 21, 2026

Reports week-80 efficacy and treatment-regimen estimates for 2,339 randomized participants, plus a selected 532-person extension and adverse-event tables.

Participants / model: Adults with obesity or overweight plus a comorbidity, without diabetes
Treatment: Weekly retatrutide 4, 9, or 12 mg or placebo; extension placebo participants switched to retatrutide
Follow-up: 80 weeks, with a selected 104-week extension
Study design: Randomized phase 3 trial with sponsor-reported extension

The 80-week efficacy and safety values and selected 104-week extension figures come from Lilly’s May 2026 disclosure rather than a full peer-reviewed phase 3 report.

Read the original source

TRIUMPH-1 · protocol and enrollment

Clinical trial registry

ClinicalTrials.gov, NCT05929066

Defines the randomized obesity population, interventions, outcomes, and trial status.

Participants / model: Adults with obesity or overweight plus a complication, without type 2 diabetes
Treatment: Retatrutide dose arms or placebo
Follow-up: Phase 3 follow-up
Study design: Randomized, parallel assignment

The registry reports trial design but not the sponsor’s outcome values.

Read the original source

Retatrutide phase 2 · obesity

Randomized trial

Jastreboff et al., New England Journal of Medicine, 2023

In 338 adults, retatrutide produced dose-dependent weight reduction over 48 weeks; gastrointestinal adverse events were the most common.

Participants / model: Adults with BMI at least 30, or at least 27 with a weight-related condition, without diabetes
Treatment: Weekly retatrutide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-blind phase 2 trial

The trial was not designed to isolate the contribution of each receptor.

Read the original source

Retatrutide · liver-fat substudy

Randomized substudy

Sanyal et al., Nature Medicine, 2024

A phase 2 substudy reported substantial liver-fat reduction, including normalization in many participants at higher doses.

Participants / model: Adults with obesity and MASLD in a retatrutide phase 2 substudy
Treatment: Weekly retatrutide or placebo
Follow-up: 24 and 48 weeks
Study design: Randomized substudy using MRI-derived liver fat

Liver-fat imaging does not isolate receptor contribution and is not the same as a biopsy-confirmed clinical outcome.

Read the original source

Why is retatrutide in S tier?

S reflects unusually large randomized weight-loss effects and a broad late-stage program. Retatrutide remains unapproved, has no trial against surgery, and products sold outside trials have no established authenticity or safety.

read Retatrutide in the reptides guide, chapter 04: 8 pages, free to read.