Evolution of liver fibrosis and steatosis markers in patients with type 2 diabetes after metformin treatment for 2 years

Background/aims: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) share pathophysiological mechanism. Metformin is a widely used first-line anti-diabetic drug. We investigated the evolution of liver fibrosis and steatosis during 2-year use of metformin in patients with T2DM. Methods: Between 2006 and August 2010, patients newly diagnosed with T2DM who received metformin as the first-line treatment were recruited. Fibrosis-4 index (FIB-4) > 2.67 and hepatic steatosis index (HSI) > 36.0 was used to define advanced liver fibrosis and fatty liver, respectively. Results: A total of 1292 (mean age 60.8 years, 57% men and 43% women) patients were recruited. The mean FIB-4 and HSI scores were 1.38 and 27.3, respectively. At enrollment, 83 (6.4%) patients had advanced liver fibrosis and 429 (33.2%) had fatty liver. After 2 years of metformin treatment, the mean FIB-4 score increased from 1.38 to 1.51 (p < 0.001), whereas the mean HSI score decreased from 27.3 to 26.5 (p < 0.001). During follow-up, advanced liver fibrosis additionally developed in 52/1209 (4.3%) patients, whereas 48/83 (57.8%) experienced fibrosis regression. Older age (odds ratio [OR] = 1.007), lower platelet count (OR = 0.993), and lower serum albumin (OR = 0.325) were independently associated with the increased risk of advanced liver fibrosis development after 2-years of metformin treatment. Conclusion: In our cohort of patients with metformin treatment, a small proportion of patients developed liver fibrosis and steatosis after 2 years. Optimized follow-up strategy is required according to different risk of liver fibrosis progression in patients with T2DM.