SGLT-2 inhibitors in nonalcoholic fatty liver disease (NAFLD)


Nonalcoholic Fatty Liver Disease (NAFLD): The Role of SGLT-2 Inhibitors

Nonalcoholic fatty liver disease (NAFLD) has emerged as a common chronic liver condition in the Western world, affecting an estimated 25-30% of the global population. This increase in prevalence is linked closely with the rise in obesity and type 2 diabetes mellitus (T2DM). NAFLD can progress to more severe conditions such as nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Despite extensive research, there is currently no approved specific treatment for NAFLD, highlighting the need for continued exploration of effective therapeutic options.

Overview of NAFLD

  • Prevalence and Impact: Affects approximately 25-30% globally, with a higher occurrence in the elderly and younger males. Post-menopause, the rates equalize between genders.
  • Histological Features: Characterized by the accumulation of liver fat in over 5% of hepatocytes, excluding other causes like excessive alcohol consumption and viral hepatitis.
  • Progression: Can evolve from simple steatosis to NASH, and potentially to cirrhosis and liver failure.
  • Extra-Hepatic Risks: Associated with increased risks of cardiovascular diseases, chronic kidney disease, and other malignancies.

Pathophysiology of NAFLD

  • Multiple-Hit Hypothesis: NAFLD development involves multiple pathogenic factors including metabolic syndromes, overnutrition, and insulin resistance, leading to lipotoxicity and oxidative stress.
  • Gut-Liver Axis: Altered gut microbiota contributes to hepatic inflammation through endotoxins and disrupted bile-acid metabolism.

Role of SGLT-2 Inhibitors in Managing NAFLD

  • Mechanism of Action: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors enhance glucose excretion in urine, aiding in glycemic control and reducing insulin levels, which may alleviate hepatic steatosis.
  • Therapeutic Potential: Early animal studies indicate potential benefits in reducing liver fat and inflammation. However, effects on liver fibrosis are less clear and require more research.

Emerging Evidence from Animal Studies

  • Dapagliflozin and Canagliflozin: Show promise in improving liver steatosis and inflammation in various animal models.
  • Empagliflozin: Exhibits potential in reducing liver fat and inflammation, with some studies suggesting dose-dependent benefits.
  • Combination Therapies: Initial studies suggest that combining SGLT-2 inhibitors with other medications might enhance therapeutic outcomes, particularly in managing fibrosis.

Challenges and Future Directions

  • Lack of Approved Treatments: Despite numerous studies, no specific therapies for NAFLD have gained approval, underscoring the complexity of its treatment.
  • Need for More Research: Both animal and clinical studies are crucial to understand the full potential and mechanisms of SGLT-2 inhibitors in NAFLD.
  • Personalized Treatment Approaches: Given the disease’s heterogeneity, a tailored approach targeting multiple pathogenic factors may be most effective.

While SGLT-2 inhibitors show promise in addressing certain aspects of NAFLD, particularly in patients with concurrent T2DM, more comprehensive studies are needed to confirm their efficacy and safety.


  1. Makri ES, Makri E, Goulas A, et al. Animal studies of sodium-glucose co-transporter 2 inhibitors in nonalcoholic fatty liver disease. Ann Gastroenterol 2024 in press
Last update: 4 May 2024, 09:19


Gastroenterologist - Hepatologist, Thessaloniki

PhD at Medical School, Aristotle University of Thessaloniki, Greece

PGDip at Universitair Medisch Centrum Utrecht, The Netherlands

Ex President, Hellenic H. pylori & Microbiota Study Group