Evolution of liver fibrosis in diabetic patients with NAFLD in a follow-up study: Hepatoprotective effects of sodium-glucose co-transporter-2 inhibitors

Background and aims: Patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are at high risk of hepatic fibrosis. To prospectively evaluate changes in fibrosis in diabetic patients with NAFLD, predisposing factors and sodium glucose cotransporter 2 inhibitors (SGLT2i) influence. Methods: 237 T2DM outpatients (mean age 67 +/- 9 years, 54% male) were enrolled and re-evaluated after 52 +/- 10 months. At baseline and follow-up NAFLD and liver fibrosis (LSM) were detected by ultrasonography and Fibroscan (R). Results: During follow-up an increase in LSM (6.0 +/- 2.8 vs 5.8 +/- 2.7 kPa, p = 0.02) and in the prescription of SGLT2i (20% vs 6%, p<0.001) was registered, despite stability of diabetic control. LSM worsened in 133(56%) subjects, 92 (39%) with worsening >10% from baseline. Patients with worsening versus non worsening of LSM had higher prevalence of increase in BMI during follow-up (45% vs 32%, p = 0.06) and lower SGLT2i prescription (15% vs 27%, p = 0.034). In multivariate analysis use of SGLT2-inhibitors at follow-up reduced the risk of LSM worsening (HR 0.34, 95% CI 0.13-0.88), even when considered>10% from baseline. Conclusions: A high prevalence of fibrosis progression was observed in diabetic subjects with NAFLD over a nearly 5-years follow up and SGLT2-inhibitors seem to reduce the risk of worsening of liver stiffness.