Comparative Hepatic Outcomes of SGLT2i or DPP4i Compared to GLP-1RA in CHB and T2DM Patients

Abstract

Background: The prevalence of diabetes is increasing among chronic hepatitis B (CHB) patients. However, the relative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) or dipeptidyl peptidase-4 inhibitors (DPP4i), compared with glucagon-like peptide-1 receptor agonists (GLP-1RA), among such at-risk populations remains unclear in terms of reducing liver-related events (LRE).

Methods: Using a nationwide database (2019-2022), we identified CHB patients with diabetes (age ≥ 40) and established two new-user cohorts: SGLT2i vs. GLP-1RA and DPP4i vs. GLP-1RA. LREs included hepatocellular carcinoma, cirrhosis, liver transplantation and liver-related mortality. For appropriate balancing, propensity score matching (PSM) was performed for each cohort. Multivariate Cox regression models were used to estimate LRE risk with adjusted hazard ratios (aHR) and 95% confidence intervals (CI).

Results: Propensity score matching provided two separate cohorts: (1) SGLT2i (n = 2297) vs. GLP-1RA (n = 461) and (2) DPP4i (n = 803) vs. GLP-1RA (n = 165) users. The LREs risk was similar across each comparison, with aHRs of 0.82 (95% CI 0.49-1.37) for GLP-1RA (vs. SGLT2i) and 0.93 (95% CI 0.41-2.07) for GLP-1RA (vs. DPP4i), indicating no significant differences. Subgroup analyses showed a trend favouring GLP-1RA over SGLT2i in females, obese individuals, antiviral therapy (AVT) users, those with diabetes complications, longer diabetes duration and physically active individuals. Compared with DPP4i, the trend was observed in AVT users and those with a shorter diabetes duration, though none were statistically significant.

Conclusion: Overall LRE risk was comparable between SGLT2i or DPP4i vs. GLP-1RA users. Further prospective studies are required to identify who can benefit from specific medication.