<b>Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors and the prevention of cirrhosis among patients with type 2 diabetes</b>

<p dir="ltr"><b>OBJECTIVE: </b>To determine whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, separately compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes.</p><p dir="ltr"><b>RESEARCH DESIGN AND METHODS: </b>With an active comparator, new user approach, we conducted a cohort study using the United Kingdom Clinical Practice Research Datalink linked with hospital and national statistics<b> </b>databases. Cox proportional hazards models employing propensity score fine stratification weighting were utilized to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cirrhosis (primary outcome), and decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality (secondary outcomes).</p><p dir="ltr"><b>RESULTS:</b> In the first cohort comparing 25,516 patients starting GLP-1 RAs and 186,752 starting DPP-4 inhibitors, GLP-1 RAs were not associated with the incidence of cirrhosis (HR 0.90, 95% CI 0.68 to 1.19) or the secondary outcomes. In a separate cohort comparing 33,161 patients starting SGLT-2 inhibitors and 124,431 starting DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced incidence of cirrhosis (HR 0.64, 95% CI 0.46 to 0.90, as also decompensated cirrhosis (HR 0.74, 95% CI 0.54 to 1.00) but not a lower risk of hepatocellular carcinoma or liver-related mortality.</p><p dir="ltr"><b>CONCLUSIONS: </b>In patients with type 2 diabetes in the UK, GLP-1 RAs were not associated with a lower risk of cirrhosis compared to DPP-4 inhibitors in patients with type 2 diabetes. However, SGLT-2 inhibitors were associated with a lower risk of cirrhosis compared to DPP-4 inhibitors.</p>