Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.

Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, Harris C

The lancet. Diabetes & endocrinology30 Jun 2025Cited by 39 (Europe PMC)

PMID40609566DOI10.1016/s2213-8587(25)00092-0PepBankPUB-40609566

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 study18

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

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, retatrutide 0.5 mg did not significantly change total fat mass versus placebo at week 36.
In plain wordsIn adults with type 2 diabetes, retatrutide 0.5 mg did not reduce body fat significantly more than placebo at week 36.
Peptide
Retatrutide
Outcome
No significant changePercent change in total fat mass at week 36
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
0.5 mg · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Percent reduction in total fat mass
4.9%
retatrutide 0.5 mg
Percent reduction in total fat mass
4.5%
placebo
LS mean difference vs placebo
−0.4 not stated
retatrutide 0.5 mg
Source sentences
Summary
Percent reduction from baseline in total fat mass was 4·9% (SE 1·4%) with retatrutide 0·5 mg, 15·2% (3·2%) with retatrutide 4 mg (pooled), 26·1% (2·5%) with retatrutide 8 mg (pooled), 23·2% (3·0%) with retatrutide 12 mg, 2·6% (1·6%) with dulaglutide, and 4·5% (1·2%) with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
-0·4 (95% CI -4·0 to 3·2, p=0·83 with retatrutide 0·5 mg
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956601
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, retatrutide 4 mg (pooled) reduced total fat mass more than placebo at week 36.
In plain wordsIn adults with type 2 diabetes, retatrutide 4 mg reduced body fat more than placebo at week 36.
Peptide
Retatrutide
Outcome
DecreasePercent change in total fat mass at week 36
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
4 mg (pooled) · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Percent reduction in total fat mass
15.2%
retatrutide 4 mg (pooled)
Percent reduction in total fat mass
4.5%
placebo
LS mean difference vs placebo
−10.7 not stated
retatrutide 4 mg (pooled)
Source sentences
Summary
Percent reduction from baseline in total fat mass was 4·9% (SE 1·4%) with retatrutide 0·5 mg, 15·2% (3·2%) with retatrutide 4 mg (pooled), 26·1% (2·5%) with retatrutide 8 mg (pooled), 23·2% (3·0%) with retatrutide 12 mg, 2·6% (1·6%) with dulaglutide, and 4·5% (1·2%) with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
-10·7 (-17·2 to -4·2, p=0·0013) with retatrutide 4 mg (pooled)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956602
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, retatrutide 8 mg (pooled) reduced total fat mass more than placebo at week 36.
In plain wordsIn adults with type 2 diabetes, retatrutide 8 mg reduced body fat more than placebo at week 36.
Peptide
Retatrutide
Outcome
DecreasePercent change in total fat mass at week 36
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
8 mg (pooled) · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Percent reduction in total fat mass
26.1%
retatrutide 8 mg (pooled)
Percent reduction in total fat mass
4.5%
placebo
LS mean difference vs placebo
−21.6 not stated
retatrutide 8 mg (pooled)
Source sentences
Summary
Percent reduction from baseline in total fat mass was 4·9% (SE 1·4%) with retatrutide 0·5 mg, 15·2% (3·2%) with retatrutide 4 mg (pooled), 26·1% (2·5%) with retatrutide 8 mg (pooled), 23·2% (3·0%) with retatrutide 12 mg, 2·6% (1·6%) with dulaglutide, and 4·5% (1·2%) with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
-21·6 (-27·1 to -16·1, p<0·0001) with retatrutide 8 mg (pooled)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956603
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, retatrutide 12 mg reduced total fat mass more than placebo at week 36.
In plain wordsIn adults with type 2 diabetes, retatrutide 12 mg reduced body fat more than placebo at week 36.
Peptide
Retatrutide
Outcome
DecreasePercent change in total fat mass at week 36
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
12 mg · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Percent reduction in total fat mass
23.2%
retatrutide 12 mg
Percent reduction in total fat mass
4.5%
placebo
LS mean difference vs placebo
−18.7 not stated
retatrutide 12 mg
Source sentences
Summary
Percent reduction from baseline in total fat mass was 4·9% (SE 1·4%) with retatrutide 0·5 mg, 15·2% (3·2%) with retatrutide 4 mg (pooled), 26·1% (2·5%) with retatrutide 8 mg (pooled), 23·2% (3·0%) with retatrutide 12 mg, 2·6% (1·6%) with dulaglutide, and 4·5% (1·2%) with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
-18·7 (-25·1 to -12·3, p<0·0001) with retatrutide 12 mg.
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956604
05HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, adverse events with retatrutide were similar between groups.
In plain wordsIn adults with type 2 diabetes, side effects with retatrutide were similar to those with placebo and dulaglutide.
Peptide
Retatrutide
Outcome
No significant changeOverall adverse events
Study
n = 189
Comparator
Placebo; dulaglutide
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
Adverse events were similar between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956607
06HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, gastrointestinal events were the most frequently reported adverse events.
In plain wordsIn adults with type 2 diabetes, the most commonly reported side effects were digestive ones.
Peptide
Retatrutide
Outcome
Not applicableGastrointestinal adverse events
Study
n = 189
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
Gastrointestinal events were the most frequently reported adverse events
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956608
07HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, no deaths were reported in the substudy.
In plain wordsIn adults with type 2 diabetes, no deaths were reported in the substudy.
Peptide
Retatrutide
Outcome
No significant changeDeaths
Study
n = 189
Outcome group
Mortality · Whole body
Studied dose
Dose not stated · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
and no deaths were reported.
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956609
08HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, serious adverse events with retatrutide 8 mg occurred at a rate similar to placebo.
In plain wordsIn adults with type 2 diabetes, serious side effects with retatrutide 8 mg occurred at a rate similar to placebo.
Peptide
Retatrutide
Outcome
No significant changeSerious adverse events
Study
n = 62
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
8 mg · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Participants with serious adverse events
9%
retatrutide 8 mg
Participants with serious adverse events
7%
placebo
Source sentences
Summary
Serious adverse events occurred in two (7%) of 29 participants in the placebo group, two (6%) of 32 participants in the retatrutide 0·5 mg group, zero of 31 participants in the retatrutide 4 mg group, three (9%) of 33 participants in the retatrutide 8 mg group, one (3%) of 30 participants in the ret…
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956612
09HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, serious adverse events with retatrutide 0.5 mg occurred at a rate similar to placebo.
In plain wordsIn adults with type 2 diabetes, serious side effects with retatrutide 0.5 mg occurred at a rate similar to placebo.
Peptide
Retatrutide
Outcome
No significant changeSerious adverse events
Study
n = 61
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
0.5 mg · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Participants with serious adverse events
6%
retatrutide 0.5 mg
Participants with serious adverse events
7%
placebo
Source sentences
Summary
Serious adverse events occurred in two (7%) of 29 participants in the placebo group, two (6%) of 32 participants in the retatrutide 0·5 mg group, zero of 31 participants in the retatrutide 4 mg group, three (9%) of 33 participants in the retatrutide 8 mg group, one (3%) of 30 participants in the ret…
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956610
10HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, no serious adverse events occurred with retatrutide 4 mg, compared with some in the placebo group.
In plain wordsIn adults with type 2 diabetes, no serious side effects occurred with retatrutide 4 mg, while placebo had some.
Peptide
Retatrutide
Outcome
No significant changeSerious adverse events
Study
n = 60
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
4 mg · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Participants with serious adverse events
0%
retatrutide 4 mg
Participants with serious adverse events
7%
placebo
Source sentences
Summary
Serious adverse events occurred in two (7%) of 29 participants in the placebo group, two (6%) of 32 participants in the retatrutide 0·5 mg group, zero of 31 participants in the retatrutide 4 mg group, three (9%) of 33 participants in the retatrutide 8 mg group, one (3%) of 30 participants in the ret…
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956611
11HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, serious adverse events with retatrutide 12 mg occurred at a rate similar to placebo.
In plain wordsIn adults with type 2 diabetes, serious side effects with retatrutide 12 mg occurred at a rate similar to placebo.
Peptide
Retatrutide
Outcome
No significant changeSerious adverse events
Study
n = 59
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
12 mg · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Participants with serious adverse events
3%
retatrutide 12 mg
Participants with serious adverse events
7%
placebo
Source sentences
Summary
Serious adverse events occurred in two (7%) of 29 participants in the placebo group, two (6%) of 32 participants in the retatrutide 0·5 mg group, zero of 31 participants in the retatrutide 4 mg group, three (9%) of 33 participants in the retatrutide 8 mg group, one (3%) of 30 participants in the ret…
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956613
12HumanRandomized controlled trialSafety outcome
In adults with diabetes, no serious adverse events occurred among 34 dulaglutide participants.
In plain wordsIn adults with diabetes, none of the 34 dulaglutide participants had serious adverse events.
Peptide
Dulaglutide (Trulicity)
Outcome
Not applicableSerious adverse events
Study
n = 34
Outcome group
Adverse events · Whole body
Studied dose
1.5 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Measurements
Serious adverse events
0 participants
dulaglutide 1.5 mg group
Source sentences
Summary
and zero of 34 participants in the dulaglutide group.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Summary · context
Eligible participants were randomly assigned in a 2:2:2:1:1:1:1:2 ratio to once-weekly subcutaneous placebo, dulaglutide 1·5 mg, or retatrutide 0·5 mg, 4 mg (2 mg initial dose), 4 mg (4 mg initial dose), 8 mg (2 mg initial dose), 8 mg (4 mg initial dose), or 12 mg.
Report a problemFND-4060956616
13HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, retatrutide improved total body fat mass reduction significantly more than dulaglutide.
In plain wordsIn adults with type 2 diabetes, retatrutide reduced body fat more than dulaglutide.
Peptide
Retatrutide
Outcome
DecreaseTotal body fat mass reduction versus dulaglutide
Study
n: not reported in source
Comparator
Dulaglutide
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
In adults with type 2 diabetes, retatrutide significantly improved total body fat mass reduction compared with placebo and dulaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956605
14HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, the proportion of lean mass loss to weight loss with retatrutide was similar to other obesity treatments.
In plain wordsIn adults with type 2 diabetes, the share of weight lost as lean mass with retatrutide was similar to other obesity treatments.
Peptide
Retatrutide
Outcome
No significant changeProportion of lean mass loss to weight loss
Study
n: not reported in source
Comparator
Other obesity treatments
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
The proportion of lean mass loss to weight loss was similar to other obesity treatments.
1 context sentence(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Report a problemFND-4060956606
15HumanRandomized controlled trialSafety outcome
In adults with diabetes, adverse events were similar across dulaglutide and other trial groups.
In plain wordsIn adults with diabetes, adverse events were similar with dulaglutide and other trial treatments.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeAdverse events
Study
n: not reported in source
Comparator
Other trial groups
Outcome group
Adverse events · Whole body
Studied dose
1.5 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
Adverse events were similar between groups.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Summary · context
Eligible participants were randomly assigned in a 2:2:2:1:1:1:1:2 ratio to once-weekly subcutaneous placebo, dulaglutide 1·5 mg, or retatrutide 0·5 mg, 4 mg (2 mg initial dose), 4 mg (4 mg initial dose), 8 mg (2 mg initial dose), 8 mg (4 mg initial dose), or 12 mg.
Report a problemFND-4060956615
16HumanRandomized controlled trialSafety outcome
In adults with diabetes, no deaths occurred in the trial, including the dulaglutide group.
In plain wordsIn adults with diabetes, no deaths occurred in the trial, including among dulaglutide recipients.
Peptide
Dulaglutide (Trulicity)
Outcome
Not applicableDeaths
Study
n: not reported in source
Outcome group
Mortality · Whole body
Studied dose
1.5 mg once weekly · subcutaneous · 36 weeksAs given in this study (human).
Source sentences
Summary
Gastrointestinal events were the most frequently reported adverse events, and no deaths were reported.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Summary · context
Eligible participants were randomly assigned in a 2:2:2:1:1:1:1:2 ratio to once-weekly subcutaneous placebo, dulaglutide 1·5 mg, or retatrutide 0·5 mg, 4 mg (2 mg initial dose), 4 mg (4 mg initial dose), 8 mg (2 mg initial dose), 8 mg (4 mg initial dose), or 12 mg.
Report a problemFND-4060956618

Studies that did not test the peptide alone2

In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Dulaglutide (Trulicity).

17HumanNot a test of Dulaglutide (Trulicity) aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, total fat mass fell from baseline in both the dulaglutide group (2.6%) and the placebo group (4.5%).
In plain wordsIn adults with diabetes, body fat fell from baseline in both the dulaglutide group (2.6%) and the placebo group (4.5%).
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseTotal fat mass reduction
Study
n: not reported in source
Analysis
Primary
Outcome group
Body composition · Metabolic and weight
Measurements
Total fat mass reduction
2.6%
dulaglutide
Standard error
1.6%
dulaglutide fat mass reduction
Total fat mass reduction
4.5%
placebo
Standard error
1.2%
placebo fat mass reduction
Source sentences
Summary
Percent reduction from baseline in total fat mass was 4·9% (SE 1·4%) with retatrutide 0·5 mg, 15·2% (3·2%) with retatrutide 4 mg (pooled), 26·1% (2·5%) with retatrutide 8 mg (pooled), 23·2% (3·0%) with retatrutide 12 mg, 2·6% (1·6%) with dulaglutide, and 4·5% (1·2%) with placebo.
3 context sentences(design, population, supporting numbers)
Summary · context
The prespecified primary substudy endpoint was percent change from baseline to week 36 in total fat mass, as measured by dual-energy X-ray absorptiometry (DXA).
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Summary · context
Eligible participants were randomly assigned in a 2:2:2:1:1:1:1:2 ratio to once-weekly subcutaneous placebo, dulaglutide 1·5 mg, or retatrutide 0·5 mg, 4 mg (2 mg initial dose), 4 mg (4 mg initial dose), 8 mg (2 mg initial dose), 8 mg (4 mg initial dose), or 12 mg.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Report a problemFND-4060956614
18HumanNot a test of Dulaglutide (Trulicity) aloneRandomized controlled trialSafety outcome
In adults with diabetes, gastrointestinal events were the most frequent adverse events across trial groups including dulaglutide.
In plain wordsIn adults with diabetes, digestive events were the most common adverse events across trial groups including dulaglutide.
Peptide
Dulaglutide (Trulicity)
Outcome
Not applicableGastrointestinal adverse events
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Source sentences
Summary
Gastrointestinal events were the most frequently reported adverse events, and no deaths were reported.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants were adults aged 18-75 years with type 2 diabetes, HbA_1c of 7·0-10·5%, stable bodyweight, and BMI of 25-50 kg/m².
Summary · context
Eligible participants were randomly assigned in a 2:2:2:1:1:1:1:2 ratio to once-weekly subcutaneous placebo, dulaglutide 1·5 mg, or retatrutide 0·5 mg, 4 mg (2 mg initial dose), 4 mg (4 mg initial dose), 8 mg (2 mg initial dose), 8 mg (4 mg initial dose), or 12 mg.
In this study, Dulaglutide (Trulicity) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dulaglutide (Trulicity).
Report a problemFND-4060956617

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 · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT04867785

A Study of LY3437943 in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 28113 May 2021 to 27 Oct 2022

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 3 Jul 2023

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.

Versions 4 to 8Current
28 Oct 2026, 02:03 UTC
The same notice was added 5 times, first on 22 Oct 2026, 02:26 UTC. The status did not change between them.
Study results updated
Version 3
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 2
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.

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