Comparative effectiveness of GLP ‐1 receptor agonists, SGLT2 inhibitors and DPP ‐4 inhibitors on liver outcomes in metabolic dysfunction‐associated steatotic liver disease: A retrospective cohort study

Jan 21, 2026Diabetes, obesity & metabolism

Comparing diabetes drugs’ effects on liver health in fatty liver disease linked to metabolism problems

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Abstract

The analysis included 4538 pairs of patients using GLP-1 receptor agonists and DPP-4 inhibitors.

No statistically significant differences in the risk of cirrhosis or hepatocellular carcinoma were observed among the different antidiabetic agents after 2 years.
Hazard ratios for GLP-1RA compared to DPP-4i were 0.80, indicating similar risk levels.
For GLP-1RA versus SGLT2i, the hazard ratio was 0.76, also suggesting no significant difference in liver-related outcomes.
The comparison between SGLT2i and DPP-4i yielded a hazard ratio of 0.78, further supporting the lack of clear distinctions among treatments.
These findings highlight that the metabolic benefits of these antidiabetic therapies may not alter the progression of liver disease in patients with MASLD and type 2 diabetes.

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AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with type 2 diabetes mellitus (T2DM). MASLD carries a substantial risk of progression to cirrhosis or hepatocellular carcinoma (HCC). Whether the metabolic benefits of antidiabetic therapy may alter this progression remains under-investigated. We aimed to evaluate the incidence of cirrhosis or HCC across the commonly used second-line antidiabetic agent classes in patients with coexisting MASLD and T2DM.

MATERIALS AND METHODS: We conducted a retrospective cohort study using healthcare claims databases in the United States. Patients with MASLD and T2DM initiating one of the three antidiabetic agent classes, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) were included. Propensity score (PS) matching was applied to control for baseline differences between treatment groups. Cumulative incidence of cirrhosis or HCC over 2 years was estimated with Kaplan-Meier method, and risks between treatment groups were compared using Cox regression.

RESULTS: The analysis included three PS-matched cohorts: 4538 GLP-1RA versus DPP-4i pairs, 4754 SGLT2i versus GLP-1RA pairs, and 4333 SGLT2i versus DPP-4i pairs. In the intention-to-treat analysis, no statistically significant differences in the risk of cirrhosis or HCC were observed at 2 years across treatment comparisons (GLP-1RA vs. DPP-4i: hazard ratios [HR] 0.80, 95% confidence intervals [CI] 0.58-1.09; GLP-1RA vs. SGLT2i: HR 0.76, 95% CI 0.55-1.04; SGLT2i vs. DPP-4i: HR 0.78, 95% CI 0.58-1.05).

CONCLUSIONS: In this large real-world study, we found no clear or consistent differences in liver-related outcomes across GLP-1RA, SGLT2i, and DPP-4i users over a 2-year period.

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Comparative effectiveness of GLP ‐1 receptor agonists, SGLT2 inhibitors and DPP ‐4 inhibitors on liver outcomes in metabolic dysfunction‐associated steatotic liver disease: A retrospective cohort study

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