Research Summary

Analyzed using Evidence Intelligence™

MK-3655 shows modest reduction in liver fat for pre-cirrhotic MASH

Last updated July 22, 2026

Key finding

Proportion of participants with MASH resolution without worsening of fibrosis was 16.7% for MK-3655 50 mg (p=0.3504).

The Phase 2b trial evaluated the safety and efficacy of MK-3655 in patients with pre-cirrhotic MASH. Results showed varying rates of MASH resolution and liver fat content reduction across different doses.

Quick read

Study at a glance

The essential study design details in one scan.

EvidenceScore™

Moderate

Study type

RCTs

Follow-up

Long-Term (1–5 y)

Risk of bias

Some Concerns

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Plain-language summary

What this paper says

A plain-language read of the study’s main message and where it applies.

Study focus

Clinical relevance

The findings are important as they explore potential treatments for patients with pre-cirrhotic MASH, a condition that can lead to severe liver damage. Understanding the efficacy of MK-3655 could guide future therapeutic strategies, although the lack of statistical significance suggests further research is needed.

Keep in mind

The study did not achieve statistical significance for primary outcomes. Sample size and population characteristics may limit generalizability. Liver fat content reduction for placebo was not reported.

Published in

Journal Reference

Publication details and source links for this paper.

Annaswamy R, Ira G, Michael C, et al. Safety and efficacy of MK-3655 in patients with pre-cirrhotic MASH: A Phase 2b trial. Alimentary Pharmacology & Therapeutics. 2025;61(7):1152-1162. doi:10.1111/apt.70038

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Main Effects

MK-3655 50 mg showed MASH resolution in 16.7% of participants (p=0.3504).

MK-3655 100 mg showed MASH resolution in 14.3% of participants (p=0.3730).

MK-3655 300 mg showed MASH resolution in 17.6% of participants (p=0.1428).

Liver fat content reduction was 19.1% for MK-3655 50 mg.

Liver fat content reduction was 26.1% for MK-3655 300 mg.

Evidence network

How this study fits

Understand where this research contributes within the broader evidence network.

Evidence Context

This study contributes evidence to HD-6277 50 mg, MK-3655 300 mg, Resmetirom (100 mg) and Liver fat content, Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH).

This study contributes evidence to

Intervention

HD-6277 50 mg

Outcome

Liver fat content

Primary intervention

HD-6277 50 mg

Primary outcomes

Liver fat content
Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Primary intervention

HD-6277 50 mg

Primary outcomes

Liver fat content Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Evidence relationships

Intervention and outcome relationships this study adds to the evidence network.

Evidence pairs

Relationships

Evidence topics

contributes_evidence

Editorial context

Why this study matters

See why this paper is useful beyond its individual results.

Evidence network role

This section describes how the study fits into the current evidence network. It does not determine whether an intervention works on its own.

Moderate contributionModerate confidenceNetwork score: 54

Why it is useful

Contributes to 6 evidence relationships
Includes primary outcome data
Linked to 0 direct semantic evidence topics

Core evidence

Study findings

The primary outcomes reported in this study.

Liver fat content

HD-6277 50 mg → Liver fat content

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

Add to Evidence Tracker

Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

HD-6277 50 mg → Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

Add to Evidence Tracker

Liver fat content

MK-3655 300 mg → Liver fat content

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

Add to Evidence Tracker

Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

MK-3655 300 mg → Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

Add to Evidence Tracker

Liver fat content

Resmetirom (100 mg) → Liver fat content

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

Add to Evidence Tracker

Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Resmetirom (100 mg) → Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

Add to Evidence Tracker

Evidence Library

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Evidence Suggest

MK-3655 300 mg led to a 26.1% reduction in liver fat content.
MASH resolution rates were 16.7% for 50 mg and 17.6% for 300 mg.
No significant differences were observed across treatment groups.

Who this applies to

Adults with pre-cirrhotic MASH.
Patients not responding to standard treatments.

Keep in Mind

Results may not be applicable to broader populations.
Further studies are needed to confirm findings.
The study's statistical limitations may affect interpretation.

Between the Lines

The study did not achieve statistical significance for primary outcomes.
Sample size and population characteristics may limit generalizability.
Liver fat content reduction for placebo was not reported.

Evidence Library

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Connected Evidence

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Relationships organized using the Dediabetes Evidence Intelligence™ framework.

This study contributes to evidence on HD-6277 50 mg and Liver fat content, HD-6277 50 mg and Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH).

Related evidence relationships

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This study contributes to the evidence on the following intervention-outcome relationships.

Medications

Detailed evidence

HD-6277 50 mg → Liver fat content

Medications

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

View evidence

Medications

Detailed evidence

HD-6277 50 mg → Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Medications

Evidence Intelligence™

EvidenceScore™: Emerging; Score 59 · Based on 1 study
ImpactScore™: 50; Neutral
ConsistencyScore™: unclear; Not enough independent studies

Based on 1 study

View evidence

Included in these evidence collections

Curated evidence collections and hubs this study is part of.

HD-6277 50 mg Evidence Hub

All studies on HD-6277 50 mg

1 studies

intervention_hub

Contributes to HD-6277 50 mg evidence base.

Liver fat content Evidence Hub

All studies measuring Liver fat content

1 studies

outcome_hub

Measures Liver fat content as a key outcome.

Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH) Evidence Hub

All studies measuring Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

1 studies

outcome_hub

Measures Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH) as a key outcome.

Recent Diabetes Research

Latest published studies

recency_collection

Published within the last 2 years.

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All studies on HD-6277 50 mg and Liver fat content

Intervention: HD-6277 50 mgOutcome: Liver fat content

1 results

All studies on HD-6277 50 mg and Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Intervention: HD-6277 50 mgOutcome: Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

1 results

All studies on HD-6277 50 mg

Intervention: HD-6277 50 mg

1 results

All studies measuring Liver fat content

Outcome: Liver fat content

1 results

All studies measuring Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

Outcome: Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)

1 results

Questions answered by this study

Generated from the study's connected evidence using Evidence Intelligence™.

Does HD-6277 50 mg improve liver fat content?

Emerging Evidence

Current evidence does not show a clear benefit of HD-6277 50 mg for Liver fat content.

ConsistencyScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
Liver fat content
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | neutral | ConsistencyScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

View Full Evidence

Does HD-6277 50 mg improve resolution of metabolic dysfunction associated steatohepatitis (mash)?

Emerging Evidence

Current evidence does not show a clear benefit of HD-6277 50 mg for Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH).

ConsistencyScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | neutral | ConsistencyScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

View Full Evidence

Does MK-3655 300 mg improve liver fat content?

Emerging Evidence

Current evidence does not show a clear benefit of MK-3655 300 mg for Liver fat content.

ConsistencyScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
Liver fat content
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | neutral | ConsistencyScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

View Full Evidence

Does MK-3655 300 mg improve resolution of metabolic dysfunction associated steatohepatitis (mash)?

Emerging Evidence

Current evidence does not show a clear benefit of MK-3655 300 mg for Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH).

ConsistencyScore™: Consistency cannot yet be determined from the available evidence.

Ranked evidence signals

1
Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)
EvidenceScore™ Emerging | EvidenceScore™ 59.0 | neutral | ConsistencyScore™ Unclear | 1 study

Why this answer: This answer is based on a single supporting study.

Limitations

Only one supporting study is available.
Consistency cannot yet be determined.
Population details are unavailable.

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All studies on HD-6277 50 mg and Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)All studies on MK-3655 300 mg and Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)All studies on Resmetirom (100 mg) and Resolution of Metabolic Dysfunction Associated Steatohepatitis (MASH)All studies on HD-6277 50 mg and Liver fat content

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