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

delete2026-08-12
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K
Kenneth Cusi
A
Amalia Gastaldelli
L
Laura Fernández Landó
P
Palash Sharma
A
Amelia Torcello‐Gómez
Á
Ángel Rodríguez *
DOI:10.1111/liv.70837delete
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Abstract

Abstract

En 中文
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.
Keywords:
fatty liver
human PNPLA3 protein
magnetic resonance imaging
single nucleotide polymorphism
tirzepatide
type 2 diabetes mellitus
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Journal

Liver International cover
Liver International
IF:
5.2
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6.6K
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1.5W

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E
Eli Lilly and Company
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lilly spain
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university of florida
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Cnr
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