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Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Nonalcoholic Fatty Liver Disease Among Patients With Type 2 Diabetes

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posted on 01.02.2022, 18:43 by Richeek Pradhan, Hui Yin, Oriana Yu, Laurent Azoulay
OBJECTIVE: To determine whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, separately, are associated with a decreased risk of non-alcoholic fatty liver disease (NAFLD), compared with dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS: We assembled two new-user, active comparator cohorts using the United Kingdom Clinical Practice Research Datalink. The first included 30,291 and 225,320 new users of GLP-1RAs and dipeptidyl peptidase-4 (DPP-4) inhibitors, respectively. The second had 41,184 and 148,421 new users of SGLT-2 inhibitors and DPP-4 inhibitors, respectively. Cox proportional hazards models weighted using propensity score fine stratification were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of NAFLD. We also determined whether the study drugs were associated with a decreased risk of hepatic transaminase elevation within restricted sub-cohorts.

RESULTS: GLP-1 RAs were associated with a lower incidence of NAFLD with a wide CI, compared with DPP-4 inhibitors (3.9 vs. 4.6 per 1000 person-years, respectively; HR 0.86, 95% CI 0.73-1.01). SGLT-2 inhibitors were associated with a decreased risk of NAFLD (5.4 vs. 7.0 per 1000 person-years, respectively; HR 0.78, 95%CI 0.68-0.89). In the restricted sub-cohorts, both GLP-1 RAs and SGLT-2 inhibitors were associated with a decreased risk of hepatic transaminase elevation (HR 0.89, 95% CI 0.83-0.95 and HR 0.66, 95% CI 0.61-0.71, respectively).

CONCLUSIONS: SGLT-2 inhibitors, and possibly GLP-1 RAs, may be associated with a decreased incidence of NAFLD and hepatic transaminase elevation among type 2 diabetes patients.


This study was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328). The sponsors had no influence on design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.