Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.

Jastreboff AM, Kaplan LM, Davies MJ, Wilding JPH, Ahmad NN, Murray M, Du Y, Makarova N, Giblin K, Schloot NC, Wang Y

The New England journal of medicine29 Sept 2026

PMID42814954DOI10.1056/nejmoa2604169PepBankPUB-42814954

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study16

16 results from studies that gave the peptide. 16 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity and knee osteoarthritis, retatrutide 9 mg reduced the WOMAC pain score more than placebo (hybrid estimand).
In plain wordsIn adults with obesity and knee osteoarthritis, retatrutide 9 mg lowered knee pain scores more than placebo.
Peptide
Retatrutide
Outcome
DecreaseWOMAC pain score change, hybrid estimand
Study
n = 574
Comparator
Placebo
Analysis
Primary
Outcome group
Pain · Musculoskeletal
Studied dose
9 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
WOMAC pain score change
−3.5 points
retatrutide 9 mg, hybrid estimand
WOMAC pain score change
−1.9 points
placebo, hybrid estimand
Difference vs placebo
−1.6 points
retatrutide 9 mg, hybrid estimand
Source sentences
Summary
Among the participants with knee osteoarthritis, the corresponding changes in the pain score in the retatrutide groups for the hybrid estimand were -3.2, -3.5, and -3.6 versus -1.9 with placebo (differences, -1.6 and -1.8 points; both P<0.001)
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495405
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity and knee osteoarthritis, retatrutide 12 mg reduced the WOMAC pain score more than placebo (hybrid estimand).
In plain wordsIn adults with obesity and knee osteoarthritis, retatrutide 12 mg lowered knee pain scores more than placebo.
Peptide
Retatrutide
Outcome
DecreaseWOMAC pain score change, hybrid estimand
Study
n = 574
Comparator
Placebo
Analysis
Primary
Outcome group
Pain · Musculoskeletal
Studied dose
12 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
WOMAC pain score change
−3.6 points
retatrutide 12 mg, hybrid estimand
WOMAC pain score change
−1.9 points
placebo, hybrid estimand
Difference vs placebo
−1.8 points
retatrutide 12 mg, hybrid estimand
Source sentences
Summary
Among the participants with knee osteoarthritis, the corresponding changes in the pain score in the retatrutide groups for the hybrid estimand were -3.2, -3.5, and -3.6 versus -1.9 with placebo (differences, -1.6 and -1.8 points; both P<0.001)
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495406
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity and knee osteoarthritis, retatrutide 9 mg reduced the WOMAC pain score more than placebo (ITT estimand).
In plain wordsIn adults with obesity and knee osteoarthritis, retatrutide 9 mg lowered knee pain scores more than placebo.
Peptide
Retatrutide
Outcome
DecreaseWOMAC pain score change, ITT estimand
Study
n = 574
Comparator
Placebo
Analysis
Primary
Outcome group
Pain · Musculoskeletal
Studied dose
9 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
WOMAC pain score change
−3.9 points
retatrutide 9 mg, ITT estimand
WOMAC pain score change
−2.5 points
placebo, ITT estimand
Difference vs placebo
−1.4 points
retatrutide 9 mg, ITT estimand
Source sentences
Summary
the corresponding changes for the ITT estimand were -3.4, -3.9, and -4.1 versus -2.5 with placebo (differences, -1.4 and -1.6 points; both P<0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495408
04HumanRandomized controlled trialEfficacy outcome
In adults with obesity and knee osteoarthritis, retatrutide 12 mg reduced the WOMAC pain score more than placebo (ITT estimand).
In plain wordsIn adults with obesity and knee osteoarthritis, retatrutide 12 mg lowered knee pain scores more than placebo.
Peptide
Retatrutide
Outcome
DecreaseWOMAC pain score change, ITT estimand
Study
n = 574
Comparator
Placebo
Analysis
Primary
Outcome group
Pain · Musculoskeletal
Studied dose
12 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
WOMAC pain score change
−4.1 points
retatrutide 12 mg, ITT estimand
WOMAC pain score change
−2.5 points
placebo, ITT estimand
Difference vs placebo
−1.6 points
retatrutide 12 mg, ITT estimand
Source sentences
Summary
the corresponding changes for the ITT estimand were -3.4, -3.9, and -4.1 versus -2.5 with placebo (differences, -1.4 and -1.6 points; both P<0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495409
05HumanRandomized controlled trialEfficacy outcome
In adults with obesity and obstructive sleep apnea, retatrutide 9 mg reduced the apnea-hypopnea index more than placebo (hybrid estimand).
In plain wordsIn adults with obesity and sleep apnea, retatrutide 9 mg cut breathing interruptions during sleep more than placebo.
Peptide
Retatrutide
Outcome
DecreaseApnea-hypopnea index change, hybrid estimand
Study
n = 243
Comparator
Placebo
Analysis
Primary
Outcome group
Sleep · Sleep
Studied dose
9 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Apnea-hypopnea index change
−34.3 events/hour
retatrutide 9 mg, hybrid estimand
Apnea-hypopnea index change
−9.9 events/hour
placebo, hybrid estimand
Difference vs placebo
−24.4 events/hour
retatrutide 9 mg, hybrid estimand
Source sentences
Summary
Among the participants with obstructive sleep apnea, the corresponding changes in events per hour in the retatrutide groups for the hybrid-treatment estimand were -22.9, -34.3, and 31.7 versus -9.9 (differences, -24.4 and -21.9; both P<0.001)
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495411
06HumanRandomized controlled trialEfficacy outcome
In adults with obesity and obstructive sleep apnea, retatrutide 12 mg reduced the apnea-hypopnea index more than placebo (hybrid estimand).
In plain wordsIn adults with obesity and sleep apnea, retatrutide 12 mg cut breathing interruptions during sleep more than placebo.
Peptide
Retatrutide
Outcome
DecreaseApnea-hypopnea index change, hybrid estimand
Study
n = 243
Comparator
Placebo
Analysis
Primary
Outcome group
Sleep · Sleep
Studied dose
12 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Apnea-hypopnea index change
−9.9 events/hour
placebo, hybrid estimand
Difference vs placebo
−21.9 events/hour
retatrutide 12 mg, hybrid estimand
Source sentences
Summary
Among the participants with obstructive sleep apnea, the corresponding changes in events per hour in the retatrutide groups for the hybrid-treatment estimand were -22.9, -34.3, and 31.7 versus -9.9 (differences, -24.4 and -21.9; both P<0.001)
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495412
07HumanRandomized controlled trialEfficacy outcome
In adults with obesity and obstructive sleep apnea, retatrutide 9 mg reduced the apnea-hypopnea index more than placebo (ITT estimand).
In plain wordsIn adults with obesity and sleep apnea, retatrutide 9 mg cut breathing interruptions during sleep more than placebo.
Peptide
Retatrutide
Outcome
DecreaseApnea-hypopnea index change, ITT estimand
Study
n = 243
Comparator
Placebo
Analysis
Primary
Outcome group
Sleep · Sleep
Studied dose
9 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Apnea-hypopnea index change
−34.3 events/hour
retatrutide 9 mg, ITT estimand
Apnea-hypopnea index change
−9.6 events/hour
placebo, ITT estimand
Difference vs placebo
−24.7 events/hour
retatrutide 9 mg, ITT estimand
Source sentences
Summary
the corresponding changes for the ITT estimand were -22.8, -34.3, and -32.1 versus -9.6 (differences, -24.7 and -22.5; both P<0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495414
08HumanRandomized controlled trialEfficacy outcome
In adults with obesity and obstructive sleep apnea, retatrutide 12 mg reduced the apnea-hypopnea index more than placebo (ITT estimand).
In plain wordsIn adults with obesity and sleep apnea, retatrutide 12 mg cut breathing interruptions during sleep more than placebo.
Peptide
Retatrutide
Outcome
DecreaseApnea-hypopnea index change, ITT estimand
Study
n = 243
Comparator
Placebo
Analysis
Primary
Outcome group
Sleep · Sleep
Studied dose
12 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Apnea-hypopnea index change
−32.1 events/hour
retatrutide 12 mg, ITT estimand
Apnea-hypopnea index change
−9.6 events/hour
placebo, ITT estimand
Difference vs placebo
−22.5 events/hour
retatrutide 12 mg, ITT estimand
Source sentences
Summary
the corresponding changes for the ITT estimand were -22.8, -34.3, and -32.1 versus -9.6 (differences, -24.7 and -22.5; both P<0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495415
09HumanRandomized controlled trialEfficacy outcome
In adults with obesity without diabetes, retatrutide 9 mg reduced body weight over 80 weeks more than placebo.
In plain wordsIn adults with obesity without diabetes, retatrutide 9 mg led to more weight loss than placebo over 80 weeks.
Peptide
Retatrutide
Outcome
DecreasePercent change in body weight
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
9 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Percent change in body weight
−23.7%
retatrutide 9 mg
Percent change in body weight
−3.9%
placebo
Difference vs placebo
−19.8 percentage points
retatrutide 9 mg
Source sentences
Summary
The mean percent change in body weight in the retatrutide groups was -17.6% (4-mg dose), -23.7% (9-mg dose), and -25.0% (12-mg dose) versus -3.9% in the placebo group (differences, -19.8 and -21.0 percentage points, respectively; P<0.001 for both comparisons).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495402
10HumanRandomized controlled trialEfficacy outcome
In adults with obesity without diabetes, retatrutide 12 mg reduced body weight over 80 weeks more than placebo.
In plain wordsIn adults with obesity without diabetes, retatrutide 12 mg led to more weight loss than placebo over 80 weeks.
Peptide
Retatrutide
Outcome
DecreasePercent change in body weight
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
12 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Percent change in body weight
−25%
retatrutide 12 mg
Percent change in body weight
−3.9%
placebo
Difference vs placebo
−21 percentage points
retatrutide 12 mg
Source sentences
Summary
The mean percent change in body weight in the retatrutide groups was -17.6% (4-mg dose), -23.7% (9-mg dose), and -25.0% (12-mg dose) versus -3.9% in the placebo group (differences, -19.8 and -21.0 percentage points, respectively; P<0.001 for both comparisons).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495403
11HumanRandomized controlled trialEfficacy outcome
In adults with obesity and knee osteoarthritis, retatrutide 4 mg reduced the WOMAC pain score more than placebo (hybrid estimand).
In plain wordsIn adults with obesity and knee osteoarthritis, retatrutide 4 mg lowered knee pain scores more than placebo.
Peptide
Retatrutide
Outcome
DecreaseWOMAC pain score change, hybrid estimand
Study
n = 574
Comparator
Placebo
Outcome group
Pain · Musculoskeletal
Studied dose
4 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
WOMAC pain score change
−3.2 points
retatrutide 4 mg, hybrid estimand
WOMAC pain score change
−1.9 points
placebo, hybrid estimand
Source sentences
Summary
Among the participants with knee osteoarthritis, the corresponding changes in the pain score in the retatrutide groups for the hybrid estimand were -3.2, -3.5, and -3.6 versus -1.9 with placebo (differences, -1.6 and -1.8 points; both P<0.001)
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495404
12HumanRandomized controlled trialEfficacy outcome
In adults with obesity and knee osteoarthritis, retatrutide 4 mg reduced the WOMAC pain score more than placebo (ITT estimand).
In plain wordsIn adults with obesity and knee osteoarthritis, retatrutide 4 mg lowered knee pain scores more than placebo.
Peptide
Retatrutide
Outcome
DecreaseWOMAC pain score change, ITT estimand
Study
n = 574
Comparator
Placebo
Outcome group
Pain · Musculoskeletal
Studied dose
4 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
WOMAC pain score change
−3.4 points
retatrutide 4 mg, ITT estimand
WOMAC pain score change
−2.5 points
placebo, ITT estimand
Source sentences
Summary
the corresponding changes for the ITT estimand were -3.4, -3.9, and -4.1 versus -2.5 with placebo (differences, -1.4 and -1.6 points; both P<0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495407
13HumanRandomized controlled trialEfficacy outcome
In adults with obesity and obstructive sleep apnea, retatrutide 4 mg reduced the apnea-hypopnea index more than placebo (hybrid estimand).
In plain wordsIn adults with obesity and sleep apnea, retatrutide 4 mg cut breathing interruptions during sleep more than placebo.
Peptide
Retatrutide
Outcome
DecreaseApnea-hypopnea index change, hybrid estimand
Study
n = 243
Comparator
Placebo
Outcome group
Sleep · Sleep
Studied dose
4 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Apnea-hypopnea index change
−22.9 events/hour
retatrutide 4 mg, hybrid estimand
Apnea-hypopnea index change
−9.9 events/hour
placebo, hybrid estimand
Source sentences
Summary
Among the participants with obstructive sleep apnea, the corresponding changes in events per hour in the retatrutide groups for the hybrid-treatment estimand were -22.9, -34.3, and 31.7 versus -9.9 (differences, -24.4 and -21.9; both P<0.001)
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495410
14HumanRandomized controlled trialEfficacy outcome
In adults with obesity and obstructive sleep apnea, retatrutide 4 mg reduced the apnea-hypopnea index more than placebo (ITT estimand).
In plain wordsIn adults with obesity and sleep apnea, retatrutide 4 mg cut breathing interruptions during sleep more than placebo.
Peptide
Retatrutide
Outcome
DecreaseApnea-hypopnea index change, ITT estimand
Study
n = 243
Comparator
Placebo
Outcome group
Sleep · Sleep
Studied dose
4 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Apnea-hypopnea index change
−22.8 events/hour
retatrutide 4 mg, ITT estimand
Apnea-hypopnea index change
−9.6 events/hour
placebo, ITT estimand
Source sentences
Summary
the corresponding changes for the ITT estimand were -22.8, -34.3, and -32.1 versus -9.6 (differences, -24.7 and -22.5; both P<0.001).
2 context sentences(design, population, supporting numbers)
Summary · context
the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495413
15HumanRandomized controlled trialEfficacy outcome
In adults with obesity without diabetes, retatrutide 4 mg reduced body weight over 80 weeks more than placebo.
In plain wordsIn adults with obesity without diabetes, retatrutide 4 mg led to more weight loss than placebo over 80 weeks.
Peptide
Retatrutide
Outcome
DecreasePercent change in body weight
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
4 mg · subcutaneous · 80 weeksAs given in this study (human).
Measurements
Percent change in body weight
−17.6%
retatrutide 4 mg
Percent change in body weight
−3.9%
placebo
Source sentences
Summary
The mean percent change in body weight in the retatrutide groups was -17.6% (4-mg dose), -23.7% (9-mg dose), and -25.0% (12-mg dose) versus -3.9% in the placebo group (differences, -19.8 and -21.0 percentage points, respectively; P<0.001 for both comparisons).
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495401
16HumanRandomized controlled trialSafety outcome
In adults with obesity without diabetes, the most common adverse events with retatrutide were gastrointestinal.
In plain wordsIn adults with obesity without diabetes, the most common side effects of retatrutide affected the digestive system.
Peptide
Retatrutide
Outcome
Not applicableGastrointestinal adverse events
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
4 mg, 9 mg, or 12 mg · subcutaneous · 80 weeksAs given in this study (human).
Source sentences
Summary
The most common adverse events were gastrointestinal.
1 context sentence(design, population, supporting numbers)
Summary · context
In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks.
Report a problemFND-4281495416

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3NCT05929066

A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight

Eli Lilly and Companyn = 2,33510 Jul 2023 to 30 Apr 2026

Obesity · Overweight · Osteoarthritis, Knee · Obstructive Sleep Apnea

Trial page ClinicalTrials.govUpdated 21 Aug 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Journal Article

PepBank is a research reference. Talk to a doctor before you use any peptide.