Safety and efficacy of 24 weeks of pemvidutide in metabolic dysfunction-associated steatotic liver disease: A randomized, controlled clinical trial.

Browne SK, Suschak JJ, Tomah S, Gutierrez JA, Yang J, Georges B, Roberts MS, Harris MS

JHEP reports : innovation in hepatology18 Jun 2025Cited by 5 (Europe PMC)

PMID41113119PMCIDPMC12529369DOI10.1016/j.jhepr.2025.101483PepBankPUB-41113119

Summary

Background & aimsThis was a double-blind 12-week extension of a randomized, placebo-controlled, 12-week trial of pemvidutide, a glucagon-like peptide-1/glucagon dual receptor agonist, in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).MethodsCompleters of a double-blind trial of pemvidutide in MASLD, who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment. Participants were stratified by the presence or absence of type 2 diabetes mellitus (T2DM). The primary efficacy endpoint was relative reduction (%) from baseline in liver fat content by magnetic resonance imaging-proton density fat fraction after 24 weeks of treatment.ResultsThere were 64 participants in the extension trial. Baseline mean values for BMI and liver fat content were 36.7 kg/m² and 22.2%; 26.6% of participants had T2DM. After 24 weeks of treatment, pemvidutide achieved relative reductions in liver fat content from baseline of 56.3%, 75.2%, and 76.4% for the pemvidutide 1.2 mg, 1.8 mg, and 2.4 mg groups respectively, vs. 14.0% for placebo (p vs. placebo, all treatment groups), with 84.6% of participants achieving 50% reductions in liver fat content and 53.8% achieving normalization (≤5% liver fat content) at the 1.8 mg dose. Body weight was also reduced by 6.2% (p vs. placebo) over 24 weeks of treatment. Pemvidutide was well-tolerated at all doses, with low incidences of side effects.ConclusionsIn individuals with MASLD, 24 weeks of pemvidutide treatment resulted in significant reductions in liver fat content and body weight that further improved upon the effects observed at 12 weeks.Impact and implicationsOverweight and obesity are strongly associated with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis (MASH), as the excess liver fat associated with obesity is a known driver of these conditions. Glucagon-like peptide-1 receptor (GLP-1R) agonists elicit weight loss through centrally and peripherally mediated effects on appetite, whereas G-coupled glucagon receptor (GCGR) agonists act directly on the liver to stimulate fatty acid oxidation and inhibit lipogenesis, providing a more potent mechanism for reducing liver fat content than weight loss alone. We previously showed that once-weekly treatment with pemvidutide, a dual GLP-1R/GCGR agonist, significantly reduced liver fat content, hepatic inflammatory activity, and body weight over 12 weeks. The current trial demonstrates that continued treatment with pemvidutide further improves these clinical markers of MASH.Clinical trials registrationThe study is registered at ClinicalTrials.gov (NCT05292911).

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

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In MASLD, pemvidutide 1.2 mg reduced liver fat by 56.3% versus 14.0% with placebo.
In plain wordsIn MASLD, pemvidutide reduced liver fat more than placebo.
Peptide
Pemvidutide
Outcome
DecreaseRelative liver fat reduction
Study
n: not reported in source
Comparator
placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
1.2 mg · subcutaneous once weekly · 24 weeksAs given in this study (human).
Measurements
Relative reduction in liver fat content from baseline
56.3%
pemvidutide 1.2 mg, week 24
Relative reduction in liver fat content from baseline
14%
placebo, week 24
Source sentences
Summary
After 24 weeks of treatment, pemvidutide achieved relative reductions in liver fat content from baseline of 56.3%, 75.2%, and 76.4% for the pemvidutide 1.2 mg, 1.8 mg, and 2.4 mg groups respectively, vs. 14.0% for placebo (p vs. placebo, all treatment groups),
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311901
02HumanRandomized controlled trialEfficacy outcome
In MASLD, pemvidutide 1.8 mg reduced liver fat by 75.2% versus 14.0% with placebo.
In plain wordsIn MASLD, pemvidutide reduced liver fat more than placebo.
Peptide
Pemvidutide
Outcome
DecreaseRelative liver fat reduction
Study
n: not reported in source
Comparator
placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
1.8 mg · subcutaneous once weekly · 24 weeksAs given in this study (human).
Measurements
Relative reduction in liver fat content from baseline
75.2%
pemvidutide 1.8 mg, week 24
Relative reduction in liver fat content from baseline
14%
placebo, week 24
Source sentences
Summary
After 24 weeks of treatment, pemvidutide achieved relative reductions in liver fat content from baseline of 56.3%, 75.2%, and 76.4% for the pemvidutide 1.2 mg, 1.8 mg, and 2.4 mg groups respectively, vs. 14.0% for placebo (p vs. placebo, all treatment groups),
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311902
03HumanRandomized controlled trialEfficacy outcome
In MASLD, pemvidutide 2.4 mg reduced liver fat by 76.4% versus 14.0% with placebo.
In plain wordsIn MASLD, pemvidutide reduced liver fat more than placebo.
Peptide
Pemvidutide
Outcome
DecreaseRelative liver fat reduction
Study
n: not reported in source
Comparator
placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
2.4 mg · subcutaneous once weekly · 24 weeksAs given in this study (human).
Measurements
Relative reduction in liver fat content from baseline
76.4%
pemvidutide 2.4 mg, week 24
Relative reduction in liver fat content from baseline
14%
placebo, week 24
Source sentences
Summary
After 24 weeks of treatment, pemvidutide achieved relative reductions in liver fat content from baseline of 56.3%, 75.2%, and 76.4% for the pemvidutide 1.2 mg, 1.8 mg, and 2.4 mg groups respectively, vs. 14.0% for placebo (p vs. placebo, all treatment groups),
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311903
04HumanRandomized controlled trialEfficacy outcome
In MASLD, 84.6% achieved a 50% liver fat reduction with pemvidutide 1.8 mg.
In plain wordsIn MASLD, most patients at this pemvidutide dose achieved the reported liver fat reduction.
Peptide
Pemvidutide
Outcome
Not applicableLiver fat reduction of 50%
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Studied dose
1.8 mg · subcutaneous once weekly · 24 weeksAs given in this study (human).
Measurements
Participants achieving 50% liver fat reduction
84.6%
pemvidutide 1.8 mg, week 24
Source sentences
Summary
with 84.6% of participants achieving 50% reductions in liver fat content and 53.8% achieving normalization (≤5% liver fat content) at the 1.8 mg dose.
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311904
05HumanRandomized controlled trialEfficacy outcome
In MASLD, 53.8% achieved liver fat normalization (≤5% liver fat content) with pemvidutide 1.8 mg.
In plain wordsIn MASLD, over half of patients at this pemvidutide dose achieved liver fat normalization.
Peptide
Pemvidutide
Outcome
Not applicableLiver fat normalization
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Studied dose
1.8 mg · subcutaneous once weekly · 24 weeksAs given in this study (human).
Measurements
Participants achieving liver fat normalization (<=5%)
53.8%
pemvidutide 1.8 mg, week 24
Source sentences
Summary
with 84.6% of participants achieving 50% reductions in liver fat content and 53.8% achieving normalization (≤5% liver fat content) at the 1.8 mg dose.
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311905
06HumanRandomized controlled trialEfficacy outcome
In MASLD, body weight decreased by 6.2% over 24 weeks with pemvidutide, with a significant difference versus placebo.
In plain wordsIn MASLD, pemvidutide reduced body weight compared with placebo.
Peptide
Pemvidutide
Outcome
DecreaseBody weight
Study
n: not reported in source
Comparator
placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · subcutaneous once weekly · 24 weeksAs given in this study (human).
Measurements
Body weight reduction
6.2%
pemvidutide, week 24
Source sentences
Summary
Body weight was also reduced by 6.2% (p vs. placebo) over 24 weeks of treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311906
07HumanRandomized controlled trialSafety outcome
In MASLD, pemvidutide was well tolerated at all doses with low incidences of side effects.
In plain wordsIn MASLD, pemvidutide was well tolerated with few side effects.
Peptide
Pemvidutide
Outcome
Not applicableSide effects and tolerability
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
1.2 mg, 1.8 mg or 2.4 mg · subcutaneous once weekly · 24 weeksAs given in this study (human).
Source sentences
Summary
Pemvidutide was well-tolerated at all doses, with low incidences of side effects.
1 context sentence(design, population, supporting numbers)
Summary · context
who were previously randomized 1:1:1:1 to pemvidutide at 1.2 mg, 1.8 mg, or 2.4 mg, or placebo administered subcutaneously once weekly for 12 weeks, were offered an additional 12 weeks of treatment at their originally assigned dose for a total of 24 weeks of treatment.
Show in the study text Report a problemFND-4111311907

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 1NCT05292911

Extension of ALT-801 in Diabetic and Non-Diabetic Overweight and Obese Subjects With (NAFLD)

Altimmune, Inc.n = 649 Mar 2022 to 31 Oct 2022

Non-Alcoholic Fatty Liver Disease

Trial page ClinicalTrials.govUpdated 27 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.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

Keywords

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