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

OBJECTIVE: 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.

RESEARCH DESIGN AND METHODS: 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 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).

RESULTS: 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.

CONCLUSIONS: 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.