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

OBJECTIVE: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, separately, are associated with a decreased risk of nonalcoholic 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 U.K. Clinical Practice Research Datalink. The first included 30,291 and 225,320 new users of GLP-1 RA and DPP-4 inhibitors, respectively. The second included 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% CIs of NAFLD. We also determined whether the study drugs were associated with a decreased risk of hepatic transaminase elevation within restricted subcohorts. RESULTS: GLP-1 RA were associated with a lower incidence of NAFLD with a wide CI compared with DPP-4 inhibitors (3.9 vs. 4.6 per 1,000 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 1,000 person-years, respectively; HR 0.78, 95% CI 0.68-0.89). In the restricted subcohorts, both GLP-1 RA 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). CONCLUSIONS: SGLT-2 inhibitors, and possibly GLP-1 RA, may be associated with a decreased incidence of NAFLD and hepatic transaminase elevation among patients with type 2 diabetes.