Similar hepatic outcome by SGLT2i vs. DPP4i for at-risk cohort with CHB & T2DM: A nationwide target trial emulation...

The prevalence of diabetes is rising among patients with chronic hepatitis B (CHB). However, the comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) in this high-risk population remains unclear. We aimed to determine if SGLT2i significantly reduces the risk of liver-related events (LREs) compared with DPP4i, using a target trial emulation approach.

We used a nationwide database to identify CHB patients with diabetes (age ≥40 years) receiving SGLT2i or DPP4i alongside metformin for ≥60 consecutive days between January 2015 and December 2020. The primary outcome was LRE, defined as hepatocellular carcinoma (HCC), liver cirrhosis (LC), transplantation, or liver-related mortality. Multivariable Cox-regression models with per-protocol analysis and propensity score matching (PSM) were performed to estimate LRE risk.

Among 16,070 patients (median age, 57 years; 66.9% male), 695 developed LREs (4.7% in SGLT2i group vs. 4.3% in DPP4i group; p=0.413). In the entire cohort, the LRE risk in the SGLT2i group was comparable to that in the DPP4i group: adjusted hazard ratio (aHR) of 0.89 (95% confidence interval [CI] 0.71-1.11). The risk of secondary outcomes in the SGLT2i group was similar to that of the DPP4i group: aHRs of 0.89 (95% CI 0.58-1.37) for HCC, 0.92 (95% CI 0.72-1.17) for LC, and 0.82 (95% CI 0.29-2.35) for all-cause mortality. These trends were consistent in the PSM cohort.

The overall hepatic prognosis was comparable between the SGLT2i and the DPP4i groups. Further prospective studies are required to reach robust conclusions.