Skip to content

Study · Randomized controlled trial · 2026

6 results

Liver Fat Changes in Patients With Type 2 Diabetes by Presence of Genetic Hepatic Steatosis: A Post Hoc Analysis of SURPASS-3 MRI.

Cusi K, Gastaldelli A, Landó LF, Sharma P, Torcello-Gómez A, Rodríguez Á

Liver international : official journal of the International Association for the Study of the Liver1 Sept 2026Cited by 1 (Europe PMC)

PMID42576670 (opens in a new tab)PMCIDPMC13458421 (opens in a new tab)DOI10.1111/liv.70837 (opens in a new tab)PepBankPUB-42576670
Download PDFPubMedAsk about this study
Jump to 6 results

Summary

The patatin-like phospholipase 3 (PNPLA3) I148M genetic variant is highly associated with steatotic liver disease. In the SURPASS-3 MRI substudy, tirzepatide significantly reduced liver fat content (LFC) versus insulin degludec in insulin-naïve patients with type 2 diabetes with metabolic dysfunction-associated steatotic liver disease. The influence of PNPLA3 I148M allele on changes in LFC in response to tirzepatide is unknown. This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment. Tirzepatide-treated participants experienced significant reductions in LFC, weight, HbA1c, and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele. Findings were consistent across genotype subgroups. In this exploratory analysis, the presence of PNPLA3 I148M allele did not seem to affect tirzepatide-induced improvement in LFC and several cardiometabolic parameters in patients with type 2 diabetes. Trial Registration: ClinicalTrials.gov identifier: NCT03882970.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes, tirzepatide significantly reduced MRI-assessed liver fat content regardless of PNPLA3 I148M allele presence.

    In plain wordsIn adults with type 2 diabetes, tirzepatide reduced liver fat whether or not people carried the PNPLA3 I148M gene variant.

    Peptide
    Tirzepatide
    Outcome
    DecreaseLiver fat content (LFC) by PNPLA3 I148M allele
    Study

    n: not reported in source

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    Dose not stated · 52 weeksAs given in this study (human).

    Source sentences

    Summary
    Tirzepatide-treated participants experienced significant reductions in LFC, weight, HbA1c, and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele.
    1 context sentence
    Summary · context
    This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes, tirzepatide significantly reduced body weight regardless of PNPLA3 I148M allele presence.

    In plain wordsIn adults with type 2 diabetes, tirzepatide reduced weight whether or not people carried the PNPLA3 I148M gene variant.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight by PNPLA3 I148M allele
    Study

    n: not reported in source

    Analysis
    Exploratory
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · 52 weeksAs given in this study (human).

    Source sentences

    Summary
    Tirzepatide-treated participants experienced significant reductions in LFC, weight, HbA1c, and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele.
    1 context sentence
    Summary · context
    This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes, tirzepatide significantly reduced HbA1c regardless of PNPLA3 I148M allele presence.

    In plain wordsIn adults with type 2 diabetes, tirzepatide lowered long-term blood sugar whether or not people carried the PNPLA3 I148M gene variant.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHbA1c by PNPLA3 I148M allele
    Study

    n: not reported in source

    Analysis
    Exploratory
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · 52 weeksAs given in this study (human).

    Source sentences

    Summary
    Tirzepatide-treated participants experienced significant reductions in LFC, weight, HbA1c, and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele.
    1 context sentence
    Summary · context
    This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes, tirzepatide treatment was followed by overall greater improvement in lipids regardless of PNPLA3 I148M allele presence.

    In plain wordsIn adults with type 2 diabetes, blood fats improved on tirzepatide whether or not people carried the PNPLA3 I148M gene variant.

    Peptide
    Tirzepatide
    Outcome
    Direction not reportedLipids by PNPLA3 I148M allele
    Study

    n: not reported in source

    Analysis
    Exploratory
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    Dose not stated · 52 weeksAs given in this study (human).

    Source sentences

    Summary
    Tirzepatide-treated participants experienced significant reductions in LFC, weight, HbA1c, and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele.
    1 context sentence
    Summary · context
    This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In adults with type 2 diabetes, tirzepatide treatment was followed by overall greater improvement in liver enzymes regardless of PNPLA3 I148M allele presence.

    In plain wordsIn adults with type 2 diabetes, liver enzymes improved on tirzepatide whether or not people carried the PNPLA3 I148M gene variant.

    Peptide
    Tirzepatide
    Outcome
    Direction not reportedLiver enzymes by PNPLA3 I148M allele
    Study

    n: not reported in source

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    Dose not stated · 52 weeksAs given in this study (human).

    Source sentences

    Summary
    Tirzepatide-treated participants experienced significant reductions in LFC, weight, HbA1c, and overall greater improvement in lipids and liver enzymes regardless of the presence of PNPLA3 I148M allele.
    1 context sentence
    Summary · context
    This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment.
  6. 06HumanRandomized controlled trialEfficacy outcome

    The presence of the PNPLA3 I148M allele did not appear to affect tirzepatide-induced improvement in liver fat content and several cardiometabolic parameters.

    In plain wordsIn adults with type 2 diabetes, carrying the PNPLA3 I148M gene variant did not seem to change how well tirzepatide worked on liver fat.

    Peptide
    Tirzepatide
    Outcome
    No significant changeEffect of PNPLA3 I148M allele on response to tirzepatide
    Study

    n: not reported in source

    Analysis
    Exploratory
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    Dose not stated · 52 weeksAs given in this study (human).

    Source sentences

    Summary
    Findings were consistent across genotype subgroups.
    2 context sentences
    Summary · context
    In this exploratory analysis, the presence of PNPLA3 I148M allele did not seem to affect tirzepatide-induced improvement in LFC and several cardiometabolic parameters in patients with type 2 diabetes.
    Summary · context
    This post hoc analysis evaluated changes in MRI-assessed LFC and cardiometabolic parameters by presence (genotypes GG and CG) or absence (genotype CC) of the PNPLA3 I148M allele after 52-week treatment.

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 3Results postedNCT03882970

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 1,4441 Apr 2019 to 4 Jan 2021

Type 2 Diabetes Mellitus

Trial pageClinicalTrials.govUpdated 19 Jan 2022

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.

  1. Version 2Current

    12 Oct 2026, 12:10 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:07 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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