Impact of SGLT2 inhibitors in comparison with DPP4 inhibitors on ascites and death in veterans with cirrhosis on metformin

Diabetes Obes Metab. 2021 Oct;23(10):2402-2408. doi: 10.1111/dom.14488. Epub 2021 Jul 28.


Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have favourable neurohumoral and metabolic effects in patients with chronic liver disease. However, studies examining SGLT2i in this population have been limited to patients with non-alcoholic fatty liver disease and have focused on surrogate biomarkers. Our aim was to evaluate whether SGLT2i can reduce the incidence of ascites and death over a period of 36 months in patients with cirrhosis and diabetes mellitus. Using electronic health data from Veterans Affairs hospitals in the United States, we conducted a propensity score matched intention-to-treat analysis among veterans on metformin who subsequently received either SGLT2i or dipeptidyl peptidase-4 inhibitors. Among 423 matched pairs (in total, 846 patients), we found no significant difference in the risk for ascites (hazard ratio 0.68 for SGLT2i, 95% confidence interval 0.37-1.25; p = .22) but did find that SGLT2i users had a reduced risk for death (adjusted hazard ratio 0.33, 95% confidence interval 0.11-0.99; p < .05). In comparison with dipeptidyl peptidase-4 inhibitors, SGLT2i may improve survival for patients with cirrhosis who require additional pharmacotherapy for diabetes mellitus beyond metformin, but confirmatory studies are necessary.

Keywords: ascites; cirrhosis; diabetes mellitus; sodium-glucose cotransporter 2 inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ascites / drug therapy
  • Ascites / epidemiology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / epidemiology
  • Metformin* / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • United States / epidemiology
  • Veterans*


  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors
  • Metformin
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4