T2D: Thiazolidinediones but Not GLP-1 Receptor Agonists Linked to Lower Risk of NAFLD

Pavankumar Kamat


August 10, 2021


  • In patients with type 2 diabetes (T2D), the current use of thiazolidinediones (TZDs) was associated with a lower risk of non-alcoholic fatty liver disease (NAFLD) compared with the current use of sulphonylureas (SUs).

  • However, the current use of glucagon-like peptide-1 (GLP-1) receptor agonists was not associated with a lower risk of NAFLD compared with the current use of insulins.

Why this matters

  • Findings support the use of TZDs for selected patients at higher risk of NAFLD but do not support previous findings concerning the beneficial effect of GLP-1 receptor agonists in this population.

Study design

  • A population-based cohort study included 207,367 patients with T2D (age, ≥18 years) from the UK Clinical Practice Research Datalink who were prescribed glucose-lowering agents and followed up for a mean of 5.1 years.

  • Primary outcome: incident NAFLD; secondary outcome: incident hepatocellular carcinoma (HCC).

  • Funding: None disclosed.

Key results

  • Patients with T2D receiving TZDs vs those receiving SUs had a lower risk of NAFLD (adjusted HR [aHR], 0.32; 95% CI, 0.20-0.51).

  • There was no difference in the risk of NAFLD between patients with T2D who were prescribed GLP-1 receptor agonists and insulin (aHR, 1.22; 95% CI, 0.91-1.63).

  • Incidence rates of HCC per 1000 person-years were:

    • 0.1 for the use of GLP-1 receptor agonists;

    • 0.4 for the use of insulins; and

    • 0.5 for combined use of GLP-1 receptor agonists and insulins.


  • Low number of NAFLD events in several subgroups may affect the generalisability of results.


van Dalem J, Driessen JHM, Burden AM, Stehouwer CDA, Klungel OH, de Vries F, Brouwers MCGJ. Thiazolidinediones and Glucagon-like Peptide-1 Receptor Agonists and the Risk of Nonalcoholic Fatty Liver Disease: A Cohort Study. Hepatology. 2021 Jun 15 [Epub ahead of print]. doi: 10.1002/hep.32012. PMID: 34129693.  View abstract 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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