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

Table 6.

Effects of Combined Treatment with Metformin and Other Antidiabetic Drugs on the Liver in Diabetic NAFLD Patients

Author (year) Populations Method of NAFLD diagnosis Design Intervention Major findings Interpretations
Body anthropometry Liver fat contents Biochemistry Liver fibrosis and histology
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 Metformin+ Rosiglitazone (n=22)

  • ↓ BMI

  • ↓ WC

 -

  • ↓ AST, ALT*

  • ↔ HbA1c

  • ↔ HOMA-IR

  • ↓ NAS*

  • ↔ Fibrosis (n=12)

 Combination of metformin and rosiglitazone improved liver enzymes and liver histology.
Choi et al. (2018)58 T2DM with NAFLD and elevated ALT (n=102) US Retrospective study Metformin+ Dapagliflozin (n=50)

  • ↓ BW

 -

  • ↓ AST*

  • ↓↓ ALT*

 - Combination of metformin and dapagliflozin was more effective in improving liver biochemistry than a combination of metformin and DPP4i.
Metformin+ Sitagliptin or Linagliptin (n=52)

  • ↔ BW

 -

  • ↓ AST*

  • ↓ ALT*

 -
Cuthbertson et al. (2012)56 T2DM and NAFLD treated with metformin (n=25) 1H MRS with IHL >5.5% Prospective single arm study Exenatide (n=19) or Liraglutide (n=6)

  • ↓ BMI

  • ↓ WC

  • ↓ IHL by 1H MRS*

  • ↔ AST

  • ↓ ALT

  • ↓ HbA1c

  • ↑ Adiponectin

 - GLP1-RA added to metformin treatment decreased liver fat content and ALT.
Yan et al. (2019)57 T2DM with NAFLD treated with metformin (n=65) MRI-PDFF >10% Randomized study Liraglutide (n=18)

  • ↓ BMI

  • ↓ WC

  • ↓ MRI-PDFF*

  • ↔ AST, ALT

  • ↓ HbA1C

  • ↓ HOMA-IR

  • ↓ Serum IL-6

  • ↔ FIB-4

  • ↔ NFS

 Combination of Metformin with liraglutide and sitagliptin reduced IHL.
Sitagliptin (n=26)

  • ↓ BMI

  • ↓ WC

  • ↓ MRI-PDFF*

  • ↓ AST, ALT

  • ↓ HbA1C

  • ↔ HOMA-IR

  • ↔ Serum IL-6

  • ↔ FIB-4

  • ↔ NFS
Insulin glargine (n=21)

  • ↔ BMI

  • ↓ WC

  • ↔ MRI-PDFF*

  • ↔ AST, ALT

  • ↓ HbA1C

  • ↔ HOMA-IR

  • ↔ Serum IL-6

  • ↔ FIB-4

  • ↔ NFS

ALT, alanine aminotransferase; AST, aspartate transaminase; BMI, body mass index; DPP4i, dipeptidyl peptidase-4 inhibitors; FIB-4, fibrosis-4 index; GLP1-RA, glucagon-like peptide-1 receptor agonists; 1H MRS, proton magnetic resonance spectroscopy; HbA1c, hemoglobin A1c; HOME-IR, homeostatic model assessment for insulin resistance; IGT, impaired glucose tolerance; IHL, intrahepatocellular lipid; IL, interleukin; MRI-PDFF, magnetic resonance imaging-estimated proton density fat fraction; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH, nonalcoholic steatohepatitis; NFS, NAFLD fibrosis score; 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.