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

Abstract

Introduction and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: The overall hepatic prognosis was comparable between the SGLT2i and the DPP4i groups. Further prospective studies are required to reach robust conclusions. (c) 2025 Fundaci & oacute;n Cl & iacute;nica M & eacute;dica Sur, A.C. Published by Elsevier Espa & ntilde;a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)