Liver international : official journal of the International Association for the Study of the LiverApr 21, 2025

Liver outcomes of SGLT2 inhibitors or DPP4 inhibitors compared to GLP-1 receptor agonists in patients with chronic hepatitis B and type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

A total of 3,265 chronic hepatitis B patients with diabetes were analyzed for liver-related event risks associated with different diabetes medications.

No significant differences in liver-related event risk were found between SGLT2 inhibitors and GLP-1 receptor agonists or between DPP4 inhibitors and GLP-1 receptor agonists.
The adjusted hazard ratios for liver-related events were 0.82 for GLP-1 receptor agonists compared to SGLT2 inhibitors and 0.93 compared to DPP4 inhibitors.
Subgroup analyses suggested a trend favoring GLP-1 receptor agonists over SGLT2 inhibitors among females, individuals with obesity, and those using antiviral therapy.
Trends were also noted for GLP-1 receptor agonists over DPP4 inhibitors in users of antiviral therapy and those with shorter diabetes duration, but none reached statistical significance.
Further prospective studies are needed to determine which patient populations may benefit from specific diabetes medications.

Simplified

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.

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Liver outcomes of SGLT2 inhibitors or DPP4 inhibitors compared to GLP-1 receptor agonists in patients with chronic hepatitis B and type 2 diabetes

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