Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML

Nature medicine10 Jun 2024Cited by 228 (Europe PMC)

PMID38858523PMCIDPMC11271400DOI10.1038/s41591-024-03018-2PepBankPUB-38858523

Summary

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760 .

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with MASLD and at least 10% liver fat, mean liver fat fell by 42.9% from baseline at 24 weeks with retatrutide 1 mg, versus +0.3% with placebo (P < 0.001).
In plain wordsIn adults with fatty liver disease, retatrutide 1 mg lowered liver fat more than placebo at 24 weeks.
Peptide
Retatrutide
Outcome
DecreaseRelative change in liver fat at 24 weeks, 1 mg
Study
n = 98
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
1 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Mean relative change in liver fat
−42.9%
1 mg, week 24
Source sentences
Summary
The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo).
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852301
02HumanRandomized controlled trialEfficacy outcome
In adults with MASLD and at least 10% liver fat, mean liver fat fell by 57.0% from baseline at 24 weeks with retatrutide 4 mg, versus +0.3% with placebo (P < 0.001).
In plain wordsIn adults with fatty liver disease, retatrutide 4 mg lowered liver fat more than placebo at 24 weeks.
Peptide
Retatrutide
Outcome
DecreaseRelative change in liver fat at 24 weeks, 4 mg
Study
n = 98
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
4 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Mean relative change in liver fat
−57%
4 mg, week 24
Source sentences
Summary
The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo).
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852302
03HumanRandomized controlled trialEfficacy outcome
In adults with MASLD and at least 10% liver fat, mean liver fat fell by 81.4% from baseline at 24 weeks with retatrutide 8 mg, versus +0.3% with placebo (P < 0.001).
In plain wordsIn adults with fatty liver disease, retatrutide 8 mg lowered liver fat more than placebo at 24 weeks.
Peptide
Retatrutide
Outcome
DecreaseRelative change in liver fat at 24 weeks, 8 mg
Study
n = 98
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
8 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Mean relative change in liver fat
−81.4%
8 mg, week 24
Source sentences
Summary
The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo).
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852303
04HumanRandomized controlled trialEfficacy outcome
In adults with MASLD and at least 10% liver fat, mean liver fat fell by 82.4% from baseline at 24 weeks with retatrutide 12 mg, versus +0.3% with placebo (P < 0.001).
In plain wordsIn adults with fatty liver disease, retatrutide 12 mg lowered liver fat more than placebo at 24 weeks.
Peptide
Retatrutide
Outcome
DecreaseRelative change in liver fat at 24 weeks, 12 mg
Study
n = 98
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
12 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Mean relative change in liver fat
−82.4%
12 mg, week 24
Source sentences
Summary
The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo).
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852304
05HumanRandomized controlled trialEfficacy outcome
In adults with MASLD, 27% of those given retatrutide 1 mg reached normal liver fat (below 5%) at 24 weeks, versus 0% with placebo.
In plain wordsIn adults with fatty liver disease, 27% on retatrutide 1 mg reached normal liver fat at 24 weeks, versus 0% on placebo.
Peptide
Retatrutide
Outcome
IncreaseNormal liver fat (<5%) at 24 weeks, 1 mg
Study
n = 98
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
1 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Participants with normal liver fat
27%
1 mg, week 24
Source sentences
Summary
At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852305
06HumanRandomized controlled trialEfficacy outcome
In adults with MASLD, 52% of those given retatrutide 4 mg reached normal liver fat (below 5%) at 24 weeks, versus 0% with placebo.
In plain wordsIn adults with fatty liver disease, 52% on retatrutide 4 mg reached normal liver fat at 24 weeks, versus 0% on placebo.
Peptide
Retatrutide
Outcome
IncreaseNormal liver fat (<5%) at 24 weeks, 4 mg
Study
n = 98
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
4 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Participants with normal liver fat
52%
4 mg, week 24
Source sentences
Summary
At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852306
07HumanRandomized controlled trialEfficacy outcome
In adults with MASLD, 79% of those given retatrutide 8 mg reached normal liver fat (below 5%) at 24 weeks, versus 0% with placebo.
In plain wordsIn adults with fatty liver disease, 79% on retatrutide 8 mg reached normal liver fat at 24 weeks, versus 0% on placebo.
Peptide
Retatrutide
Outcome
IncreaseNormal liver fat (<5%) at 24 weeks, 8 mg
Study
n = 98
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
8 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Participants with normal liver fat
79%
8 mg, week 24
Source sentences
Summary
At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852307
08HumanRandomized controlled trialEfficacy outcome
In adults with MASLD, 86% of those given retatrutide 12 mg reached normal liver fat (below 5%) at 24 weeks, versus 0% with placebo.
In plain wordsIn adults with fatty liver disease, 86% on retatrutide 12 mg reached normal liver fat at 24 weeks, versus 0% on placebo.
Peptide
Retatrutide
Outcome
IncreaseNormal liver fat (<5%) at 24 weeks, 12 mg
Study
n = 98
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
12 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Measurements
Participants with normal liver fat
86%
12 mg, week 24
Source sentences
Summary
At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852308
09HumanRandomized controlled trialMechanism
In adults with MASLD given retatrutide, liver fat reductions were significantly related to changes in body weight.
In plain wordsIn adults with fatty liver disease on retatrutide, bigger liver fat reductions were linked to bigger changes in body weight.
Peptide
Retatrutide
Outcome
Not applicableLiver fat reduction vs change in body weight
Study
n = 98
Outcome group
Liver fat and liver function · Liver
Studied dose
1, 4, 8 or 12 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852309
10HumanRandomized controlled trialMechanism
In adults with MASLD given retatrutide, liver fat reductions were significantly related to changes in abdominal fat.
In plain wordsIn adults with fatty liver disease on retatrutide, bigger liver fat reductions were linked to bigger changes in abdominal fat.
Peptide
Retatrutide
Outcome
Not applicableLiver fat reduction vs change in abdominal fat
Study
n = 98
Outcome group
Liver fat and liver function · Liver
Studied dose
1, 4, 8 or 12 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852310
11HumanRandomized controlled trialMechanism
In adults with MASLD given retatrutide, liver fat reductions were significantly related to metabolic measures of improved insulin sensitivity.
In plain wordsIn adults with fatty liver disease on retatrutide, bigger liver fat reductions were linked to better insulin sensitivity measures.
Peptide
Retatrutide
Outcome
Not applicableLiver fat reduction vs insulin sensitivity measures
Study
n = 98
Outcome group
Liver fat and liver function · Liver
Studied dose
1, 4, 8 or 12 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852311
12HumanRandomized controlled trialMechanism
In adults with MASLD given retatrutide, liver fat reductions were significantly related to metabolic measures of improved lipid metabolism.
In plain wordsIn adults with fatty liver disease on retatrutide, bigger liver fat reductions were linked to better lipid metabolism measures.
Peptide
Retatrutide
Outcome
Not applicableLiver fat reduction vs lipid metabolism measures
Study
n = 98
Outcome group
Liver fat and liver function · Liver
Studied dose
1, 4, 8 or 12 mg once weekly · subcutaneous · 48 weeksAs given in this study (human).
Source sentences
Summary
LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism.
2 context sentences(design, population, supporting numbers)
Summary · context
The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF.
Summary · context
Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo.
Show in the study text Report a problemFND-3885852312

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 postedNCT04881760

A Study of LY3437943 in Participants Who Have Obesity or Are Overweight

Eli Lilly and Companyn = 33820 May 2021 to 22 Nov 2022

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 13 Sept 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.

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

MeSH terms

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