Sodium-glucose linked transporter 2 inhibitors in liver cirrhosis: Beyond their antidiabetic use

Liver Int. 2024 Apr;44(4):884-893. doi: 10.1111/liv.15851. Epub 2024 Jan 31.

Abstract

Type 2 diabetes mellitus (T2DM) and liver cirrhosis are clinical entities that frequently coexist, but glucose-lowering medication options are limited in cirrhotic patients. Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a class of glucose-lowering medication that act independently of insulin, by causing glycosuria in the proximal convoluted tubule. In this review, we aimed to briefly present the main data and to provide insight into the pathophysiology and potential usefulness of SGLT2 inhibitors in cirrhotic patients with or without T2DM. SGLT2 inhibitors have been proven useful as antidiabetic treatment in patients with metabolic liver disease, with most robust data from patients with metabolic dysfunction-associated steatotic liver disease (MASLD), where they also showed improvement in liver function parameters. Moreover, it has been suggested that SGLT2 inhibitors may have effects beyond their antidiabetic action. Accordingly, they have exhibited cardioprotective effects, expanding their indication in patients with heart failure without T2DM. Since decompensated liver cirrhosis and congestive heart failure share common pathophysiological features, namely renin-angiotensin-aldosterone axis and sympathetic nervous system activation as well as vasopressin secretion, SGLT2 inhibitors could also be beneficial in patients with decompensated cirrhosis, even in the absence of T2DM.

Keywords: SGLT2 inhibitor; cirrhosis; diabetes; heart failure; natriuresis.

Publication types

  • Review

MeSH terms

  • Canagliflozin / therapeutic use
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose / metabolism
  • Glucosides / pharmacology
  • Glucosides / therapeutic use
  • Heart Failure*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Hypoglycemic Agents
  • Canagliflozin
  • Glucosides
  • Glucose
  • Sodium