Sodium Glucose Co-Transporter 2 Inhibitors Use in Diabetic Patients with Cirrhosis Improves Liver-related Outcomes and Survival

Background: The liver outcomes of SGLT-2 inhibitor (SGLT-2i) in T2DM patients with cirrhosis have not been well studied. Methods: We conducted a retrospective cohort study (January 1, 2010–December 31, 2025) using two databases. Adults ≥ 18 years with type 2 diabetes mellitus (T2DM) and cirrhosis newly treated with SGLT-2i were identified. Patients were grouped into those receiving SGLT-2i and those not receiving SGLT-2i. Baseline characteristics were compared before and after propensity score matching. The primary outcome was the incidence of hepatic decompensation among SGLT-2i users versus non-users. Results: The intervention group consisted of 14,231 SGLT-2i users and the control group consisted of 249,746 non-SGLT-2i users. After 1:1 PSM, use of SGLT-2i was associated with reduced composite outcome of hepatic decompensation compared to control group at 1 year (9.9% vs. 12.5%, p=0.001), at 3 years (16.4% vs. 18.1%, p<0.001) and 5 years (19.9% vs 21.9%, p<0.001). HCC rates were significantly lower in the SGLT-2i users at 1 year (2.3% vs. 3.5%, p=0.001), at 3 years (2.9% vs. 4.2%, p=0.001) and at 5 years (3.4% vs. 4.8%, p=0.001). There was a 31% reduction in mortality in the SGL-T2i arm (HR: 0.69; CI: 0.56- 0.83, p<0.001), as compared to the non-SGLT-2i arm. These findings were validated in the EVERSANA database. Conclusions: Use of SGLT-2i was associated with a reduced composite outcome of hepatic decompensation and mortality among patients with T2DM and cirrhosis compared with non–SGLT-2i users across two independent datasets. Prospective randomized controlled trials are needed to confirm these findings.