Effect of SGLT-2 Inhibitors in Patients With T2DM and Moderate to Severe Liver Fibrosis
Condition: Type2diabetes
MeSH terms: Liver Cirrhosis; Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      This retrospective study will be of 12 months duration where 40 T2DM patients coming to
      FORTIS C-DOC hospital in OPD with F3 fibrosis will be included in the study. The population
      will be representative of different socio-economic strata of the society. Clinical and
      dietary profiles, phenotypic markers (acanthosis nigricans, buffalo hump, skin tags,
      xanthelasma, double chin, arcus, hirsutism) anthropometric assessments body mass index;
      biochemical markers like liver function test, HbA1c, prothrombin time/INR, and fibroscan will
      be assessed.
    

Detailed description: 
      Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease
      worldwide. Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD)
      commonly exist together. The presentations of NAFLD range from simple steatosis (NAFL),
      nonalcoholic steatohepatitis (NASH), and cirrhosis. NAFLD has a prevalence of 70% among T2DM
      patients. This results in adverse outcomes such as higher rates of mortality due to
      cirrhosis. Cirrhosis and liver failure occurs in 11%-20% in NASH patients. Overweight/obesity
      and insulin resistance (IR) have been strongly linked with NAFLD. Patients with diabetes or
      prediabetes had progressive fibrosis when their serial biopsies were studied. Those patients
      with worsening metabolic risk factors tend to have increased progression from NAFL to NASH
      and fibrosis.

      Non-invasive assessment of disease are based on clinical parameters such as age, sex, liver
      function test, platelet count, lipid profile, body mass index (BMI), and imaging modalities
      such as ultrasound (USG), transient Elastography (TE), and magnetic resonance imaging (MRI)
      mass spectroscopy. Fibrosis stage is recognized as the most objective indicator of liver
      damage and is the best prognostic marker for morbidity and mortality in liver disease of
      various etiologies. The rise in the incidence of nonalcoholic steatohepatitis (NASH) has
      necessitated the development of an effective prevention methodology.

      Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are glucose-lowering agents that
      improve glucose control while promoting weight loss and lowering serum uric acid levels.
      These agents may exert cardiovascular and renal protection in T2DM patients with established
      cardiovascular disease. Recent findings from both randomized controlled trials and open-label
      studies have also shown that SGLT2 inhibitors are able to reduce fatty liver content, as
      assessed by different imaging techniques, and improve biological markers of NAFLD, especially
      serum liver enzymes, in patients with T2DM. In addition, there are emerging data to suggest a
      mechanism beyond the reduction of hyperglycaemia and body weight, and a potential role for
      the decrease in low-grade inflammation and oxidative stress associated with SGLT2 inhibitor
      therapy. This positive effect of SGLT2 inhibitors on NAFLD complements their already
      well-known effects on cardiovascular and chronic kidney diseases.

      SGLT2 inhibitors significantly reduced liver fat when added to the standard treatment for
      T2DM. There are very few studies which have examined the effects of SGLT2 inhibitors in
      patients with F3 fibrosis. In a randomized controlled trail addition of 5mg/d
      dapagliflozin(SGLT2 inhibitor) for 24 weeks decreased liver stiffness measure from 14.7 to 11
      kPa and also reduced visceral fat. In a prospective non-randomized study 100mg canagliflozin
      (SGLT-2 inhibitor) administered once daily for 12 months significantly reduced hepatic fat
      17.6 to 12 after 6 months measured by magnetic resonance imaging. It also reduced body fat
      and improved liver enzymes. Another study showed reduction in patients with F4 fibrosis with
      exenatide once weekly and dapagliflozin once daily at 28 weeks.
    

Observational model: Other
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        T2DM patients visiting Fortis CDOC hospital and diagnosed with Moderate/Severe fibrosis
        were included.