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. 2021 Nov 15;15(6):827–840. doi: 10.5009/gnl20367

Table 4.

Effects of Metformin on the Liver in Diabetic NAFLD Patients

Author (year) Populations Method of NAFLD diagnosis Design Metformin, PO (dose/duration) Major findings (compared to baseline) Interpretations
Body anthropometry Liver fat contents Biochemistry Liver fibrosis and histology
Studies showing benefit of metformin use
Fan et al. (2013)47 T2DM with NAFLD (n=68) US Randomized study 1,000-2,000 mg/day/12 weeks

  • ↓ BMI

 -

  • ↓ AST, ALT*

  • ↓ HbA1c

  • ↓ HOMA-IR

 - Metformin was able to improve hepatic enzymes.
Feng et al. (2017)48 T2DM with NAFLD (n=29) Quantitative US with IHF ≥10% Randomized open-label study 2,000 mg/day/24 weeks

  • ↓ BMI

  • ↓ WC

  • ↓ IHF*

  • ↓ AST, ALT*

  • ↓ HbA1c*

 - Metformin decreased liver aminotransferase level and hepatic fat content.
Zhang et al. (2017)46 T2DM with NAFLD (n=50) CT (L/S CT ratio <1) Randomized study 1,500 mg/day/24 weeks

  • ↓ BMI

  • ↑ L/S CT ratio

  • ↓ AST, ALT

  • ↓ HbA1c

  • ↓ HOMA-IR

  • ↓ LSM

 Metformin was effective in reducing liver enzymes, fat content and hepatic fibrosis.
Yabiku et al. (2017)49 Male T2DM with NAFLD (n=92) US Randomized study 1,000 mg/days/24 weeks

  • ↓ BMI

  • ↑ L/S CT ratio*

  • ↓ AST, ALT

  • ↓ HOMA-IR

 - Metformin improved liver enzymes and hepatic fat content.
Tian et al. (2018)50 T2DM with NAFLD (n=75) US Randomized study 1,000-1,500 mg/day/ 12 weeks

  • ↓ BMI

 -

  • ↓AST, ALT

  • ↓ HbA1c

  • ↓ HOMA-IR

 - Metformin decreased liver enzymes.
Zsóri et al. (2019)53 New-onset T2DM (n=11) CT Prospective study 1,000 mg/day/16 weeks

  • ↔ BMI

 ↑ CT radiation absorption*

  • ↔ HbA1c

  • ↔ HOMA-IR

 - Metformin treatment lowered the amount of fat in the liver of patients with new-onset T2DM.
Studies showing uncertain/negative results of metformin use
Omer et al. (2010)51 T2DM or IGT with NASH and elevated ALT (n=22) Histologic diagnosis of NASH (NAS ≥5) Open-label randomized study 1,700 mg/day/48 weeks

  • ↓ BMI

  • ↓ WC

 -

  • ↔ AST, ALT*

  • ↔ HbA1c

  • ↔ HOMA-IR

  • ↔ NAS*

  • ↔ Fibrosis (n=10)

 Metformin did not improve transaminase levels and histological NASH score.
Shibuya et al. (2018)52 T2DM with NAFLD (n=16) US or CT Randomized open-label study 1,500 mg/day/24 weeks

  • ↔ BMI

  • ↓ L/S CT ratio*

  • ↔ ALT

  • ↔ HbA1c

 - Metformin had no beneficial effects on transaminase level and hepatic fat content.

ALT, alanine aminotransferase; AST, aspartate transaminase; BMI, body mass index; HbA1c, hemoglobin A1c; HOME-IR, homeostatic model assessment for insulin resistance; IGT, impaired glucose tolerance; IHF, intrahepatic fat; L/S CT ratio, liver/spleen liver/spleen computed tomography (CT) ratio; LSM, liver stiffness measurement; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH, nonalcoholic steatohepatitis; PO, per os; T2DM, type 2 diabetes mellitus; US, ultrasonography; WC, waist circumference; ↓, significant decrease; ↑, significant increase; ↔, no significant change.

*An asterisk symbol in the major finding column indicates the primary outcomes in that report.