SGLT2 Inhibitor Use and Cardiorenal Outcomes in Type 2 Diabetes With Liver Cirrhosis

Type 2 diabetes (T2D) and liver cirrhosis frequently coexist, creating a high-risk population for adverse outcomes. Patients with both conditions face elevated risks of kidney and cardiovascular complications, yet evidence regarding optimal antidiabetic therapy in this vulnerable population remains limited.

To evaluate the association of sodium-glucose cotransporter-2 inhibitor (SGLT2i) vs dipeptidyl peptidase-4 inhibitor (DPP4i) use with kidney outcomes, cardiovascular events, and hepatic decompensation in patients with concurrent T2D and liver cirrhosis.

This nationwide retrospective cohort study utilized data from the Taiwan's National Health Insurance Database between May 2016 and December 2023. Adults with both T2D and liver cirrhosis who initiated either SGLT2is or DPP4is were included.

Use of SGLT2is (dapagliflozin, empagliflozin, and canagliflozin) or DPP4is (alogliptin, linagliptin, sitagliptin, saxagliptin, and vildagliptin).

The primary outcomes were end-stage kidney disease (ESKD), acute kidney injury (AKI), and major adverse cardiovascular events (MACE). Secondary outcomes included individual MACE components and hepatic decompensation events. Inverse probability of treatment weighting was employed to balance baseline characteristics.

Among 24 259 patients (mean [SD] age, 64.68 [11.95] years; 8229 female [33.92%]), 9689 (39.94) received SGLT2is and 14 570 (60.06%) received DPP4is. During a median (IQR) follow-up of 2.3 (1.0-4.0) years, compared with DPP4i use, SGLT2i treatment was associated with significantly reduced risks of ESKD (adjusted hazard ratio [HR], 0.34; 95% CI, 0.25-0.47), AKI (adjusted HR, 0.66; 95% CI, 0.59-0.74), and MACE (adjusted HR, 0.67; 95% CI, 0.62-0.71). Additionally, SGLT2i use was associated with a lower risk of all-cause mortality (adjusted HR, 0.58; 95% CI, 0.53-0.63) and hepatic decompensation events (adjusted HR, 0.65; 95% CI, 0.57-0.74).

In this cohort study of patients with T2D and liver cirrhosis, the use of SGLT2is was associated with substantially lower risks of adverse kidney, cardiovascular, and hepatic outcomes compared with DPP4is. These findings suggested significant cardiorenal and hepatic protection for SGLT2is in this high-risk population.