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This study focuses on the association between the risk of the development of nonalcoholic fatty liver disease (NAFLD) and the use of thiazolidinediones (TZDs) and glucagon-like peptide-1 (GLP-1) receptor agonists compared with the use of insulin and sulfonylureas (SUs). In addition, the incidence of hepatocellular carcinoma (HCC) in users of TZDs and GLP-1 receptor agonists was calculated. NAFLD risk was lower in patients prescribed TZDs compared with those prescribed SUs (aHR, 0.32); however, no difference was seen between users of GLP-1 receptor agonists compared with users of insulin (aHR, 1.22). Crude incidence rates of HCC per 1000 person-years were 0.3 for the use of TZDs, 0.1 for GLP-1 receptor agonists, 0.3 for SUs, 0.4 for insulin, 0.2 for a combination of TZDs and SUs, and 0.5 for a combination of GLP-1 receptor agonists and insulin.
The results of this study support the use of TZDs for selected patients at risk of NAFLD, provided contraindications and side-effects are considered. However, they do not support the beneficial effect of GLP-1 receptor agonists.
Thiazolidinediones (TZDs) and glucagon-like peptide-1 (GLP-1) receptor agonists are potential pharmacological treatment options for patients at risk of NAFLD. Therefore, we examined the association between the risk of NAFLD and the use of TZDs and GLP-1 receptor agonists compared with the use of sulfonylureas (SUs) and insulins. Additionally, we calculated the incidence of HCC in users of TZDs and GLP-1 receptor agonists.
APPROACH AND RESULTS
We conducted a population-based cohort study using primary care data from the Clinical Practice Research Datalink database (2007-2018). All patients aged ≥18 with a prescription of an oral glucose-lowering agent or GLP-1 receptor agonist were included. The first prescription defined the start of follow-up. The primary outcome was a new diagnosis of NAFLD. Cox proportional hazards regression was used to estimate HRs and 95% CIs of the primary outcome. Incidence rates of HCC were determined per 1,000 person-years for all exposures. The study identified 207,367 adults with a prescription for a glucose-lowering agent. The risk of NAFLD was lower in patients prescribed a TZD than in those prescribed an SU (adjusted HR [aHR], 0.32; 95% CI, 0.20-0.51). No difference in risk of NAFLD was observed comparing GLP-1 receptor agonist use with insulin use (aHR, 1.22; 95% CI, 0.91-1.63).
Results of our study endorse the use of TZDs for selected patients at risk of NAFLD but do not support previous findings regarding the beneficial effect of GLP-1 receptor agonists. The low number of events in several subgroups may affect the generalizability of the current findings.