Tirzepatide Shows Potential to Improve Fatty Liver Associated Fibrosis in Diabetes: Insights from the SURPASS-3 MRI Substudy

Review by Prof. Cinthia Reyes Cruz (USA)

Study Summary 

We already know that nonalcoholic fatty liver disease (NAFLD) is common in people with type 2 diabetes (T2DM), but treatment options specifically targeting liver fat and fibrosis are still lacking. Glucagon-like peptide-1 (GLP-1) receptor agonists have shown some promise in reducing liver fat, but their effects on liver fibrosis aren’t well established. The SURPASS-3 MRI substudy looked at tirzepatide, a new drug that activates receptors for both incretins, gastric inhibitory peptide (also known as glucose-independent insulinotropic peptide) GIP and GLP-1, to see how it affects liver fat and fibrosis markers in adults with T2DM who had significant liver fat at baseline.

In this study, 296 participants had their liver fat and fibrosis assessed by two magnetic resonance imaging (MRI) techniques, MRI-proton density fat fraction (MRI-PDFF) and MRI corrected T1 (MRI, cT1). After 52 weeks, tirzepatide caused a dose-dependent drop in liver fat—up to a 55% relative reduction—and many patients’ liver fat normalized. The cT1 results also improved, suggesting potential benefits in reducing liver inflammation and fibrosis risk.

Commentary 

This trial is quite impressive. It was randomized and used reliable imaging to show that tirzepatide not only improves blood sugar and weight but also tackles the liver disease that often comes with diabetes. Using MRI instead of liver biopsies makes it easier and safer to track changes. In terms of study limitations, there is no biopsy data confirming these findings. And the follow-up period was just one year, which might be too short to see long-term fibrosis changes. Although, it is still promising to see these changes with non-invasive accessible tests.

The study population reflects what we commonly see in clinical practice, but the advanced imaging and cost of this new medication might limit how widely this can be applied worldwide. Overall, these findings open the door for incretin-based therapies in managing fatty liver disease, but we’ll need longer and bigger studies with liver biopsies to really confirm if tirzepatide can really stop or even reverse fibrosis.

Citation

PubMed Link: https://pubmed.ncbi.nlm.nih.gov/35499741/

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