Study wrapper · #1183
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, et al. Liver international : official journal of the International Association for the Study of the Liver. 2026.
DOI: 10.1111/liv.70837PubMed: 42576670
Editor's note
This post hoc look at SURPASS-3 MRI asks whether the strongest known genetic driver of fatty liver blunts tirzepatide's effect on liver fat. It does not appear to: reductions in liver fat content, weight, HbA1c, lipids, and liver enzymes held up across PNPLA3 genotype subgroups at 52 weeks. As an exploratory subanalysis it cannot carry the weight of a primary endpoint, but the consistency across genotypes is a reassuring signal for tirzepatide's liver effects.
Plain-language abstract
A common gene variant, PNPLA3 I148M, raises the risk of fatty liver disease. This analysis of the SURPASS-3 MRI trial found that tirzepatide reduced liver fat, weight, and blood sugar over 52 weeks whether or not patients carried the variant.
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