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Abstract Details
Thiazolidinediones and Glucagon-like Peptide-1 Receptor Agonists and the Risk of Nonalcoholic Fatty Liver Disease: A Cohort Study
Hepatology. 2021 Jun 15. doi: 10.1002/hep.32012. Online ahead of print.
Judith van Dalem12, Johanna H M Driessen1234, Andrea M Burden5, Coen D A Stehouwer26, Olaf H Klungel3, Frank de Vries123, Martijn C G J Brouwers27
Author information
1Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre+, Maastricht, the Netherlands.
2CARIM School for Cardiovascular Disease, Maastricht University, Maastricht, the Netherlands.
3Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, the Netherlands.
4NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
5Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
6Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.
7Department of Internal Medicine, Division of Endocrinology and Metabolic Disease, Maastricht University Medical Centre+, Maastricht, the Netherlands.
Abstract
Thiazolidinediones (TZDs) and glucagon-like peptide-1 (GLP-1) receptor agonists are potential pharmacological treatment options for patients at risk of nonalcoholic fatty liver disease (NAFLD). Therefore, we examined the association between the risk of NAFLD and the use of thiazolidinediones and GLP-1 receptor agonists compared with the use of sulfonylureas (SUs) and insulins. Additionally, we calculated the incidence of hepatocellular carcinoma (HCC) in users of TZDs and GLP-1 receptor agonists. We conducted a population-based cohort study using primary care data from the Clinical Practice Research Datalink (CPRD) 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 hazard ratios (HRs) and 95% confidence intervals (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 thiazolidinedione than in those prescribed a 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). Conclusion: 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.