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Background <p>Sodium-glucose cotransporter-2 (SGLT-2) inhibitors with pleiotropic effects beyond glycemic control potentially improve clinical outcomes in cirrhosis; however, large-scale human evidence remains limited. We aimed to compare liver outcomes and mortality risk in adults with type 2 diabetes and compensated cirrhosis, who initiated either SGLT-2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors.</p> Methods <p>Using the TriNetX Global Collaborative Network and a target trial emulation framework, we identified adults with compensated cirrhosis and type 2 diabetes initiating an SGLT-2- or DPP-4 inhibitor between 2016 and 2024. Baseline demographics, laboratory information, comorbidities and concomitant medications were matched by propensity scores. The primary outcome was a composite of incident hepatic decompensation, hepatocellular carcinoma and all-cause mortality. We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CI).</p> Results <p>We included 5,398 patients (mean [SD] age: 63.9 [10.3] years), receiving SGLT-2 inhibitors, matched to 5,398 DPP-4 inhibitor users, with an overall mean follow-up of 49.8&#xa0;months. Compared to DPP-4 inhibitors, SGLT-2 inhibitors were associated with a lower risk of the primary composite outcome (HR: 0.85, 95% CI: 0.79–0.91), with similar results for all-cause mortality (HR: 0.77, 95% CI: 0.69–0.85) and incident hepatic decompensation (HR: 0.89, 95% CI: 0.82–0.96), but not for hepatocellular carcinoma (HR: 0.96, 95% CI: 0.82–1.14).</p> Conclusions <p>Among adults with compensated cirrhosis and type 2 diabetes, SGLT-2 inhibitors were associated with lower risk of all-cause mortality and incident hepatic decompensation, compared to DPP-4 inhibitors. Future clinical trials are warranted to confirm this observation.</p>

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SGLT-2 Inhibitor use and liver-related and mortality outcomes in patients with type 2 diabetes and compensated cirrhosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月12日

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  • Tien-Shin Chou,
  • Daniel Hsiang-Te Tsai,
  • Shieh-Chieh Shao,
  • Edward Chia-Cheng Lai

摘要

Background

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors with pleiotropic effects beyond glycemic control potentially improve clinical outcomes in cirrhosis; however, large-scale human evidence remains limited. We aimed to compare liver outcomes and mortality risk in adults with type 2 diabetes and compensated cirrhosis, who initiated either SGLT-2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors.

Methods

Using the TriNetX Global Collaborative Network and a target trial emulation framework, we identified adults with compensated cirrhosis and type 2 diabetes initiating an SGLT-2- or DPP-4 inhibitor between 2016 and 2024. Baseline demographics, laboratory information, comorbidities and concomitant medications were matched by propensity scores. The primary outcome was a composite of incident hepatic decompensation, hepatocellular carcinoma and all-cause mortality. We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CI).

Results

We included 5,398 patients (mean [SD] age: 63.9 [10.3] years), receiving SGLT-2 inhibitors, matched to 5,398 DPP-4 inhibitor users, with an overall mean follow-up of 49.8 months. Compared to DPP-4 inhibitors, SGLT-2 inhibitors were associated with a lower risk of the primary composite outcome (HR: 0.85, 95% CI: 0.79–0.91), with similar results for all-cause mortality (HR: 0.77, 95% CI: 0.69–0.85) and incident hepatic decompensation (HR: 0.89, 95% CI: 0.82–0.96), but not for hepatocellular carcinoma (HR: 0.96, 95% CI: 0.82–1.14).

Conclusions

Among adults with compensated cirrhosis and type 2 diabetes, SGLT-2 inhibitors were associated with lower risk of all-cause mortality and incident hepatic decompensation, compared to DPP-4 inhibitors. Future clinical trials are warranted to confirm this observation.