Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial.
OBJECTIVE
The antidiabetic agent metformin is regularly discussed as a promising treatment for non-alcoholic fatty liver disease (NAFLD), which is characterized by insulin resistance. However, the evidence for its beneficial effects is limited, and conflicting reports have been published. The purpose of this study was to conduct a randomized, double-blind, placebo-controlled trial to test whether metformin improves liver histology in patients with non-alcoholic fatty liver disease.


METHODS
Forty-eight patients with biopsy-proven NAFLD were randomized to treatment with metformin (n=24) or placebo (n=24) for 6 months. A second liver biopsy was obtained in all subjects who completed the trial (n=44). Data analyses are restricted to this group (per-protocol analyses). The primary outcome was changes in histologically assessed liver steatosis. Secondary outcomes were changes in NAFLD activity (NAS)-score, liver steatosis assessed by computed tomography (CT), liver transaminases, body-weight, metabolic variables and inflammatory markers.


RESULTS
No significant differences between treatment with metformin or placebo were observed for changes in liver steatosis, assessed either histologically or by CT, NAS-score, liver transaminases or on markers of insulin resistance or inflammation. In contrast, beneficial effects of metformin were observed on changes in body-weight (p<0.001), serum levels of cholesterol (p=0.004), LDL-cholesterol (p<0.001), glucose (p=0.032) and on HbA1c (p=0.020).


CONCLUSIONS
Treatment with metformin for 6 months was no better than placebo in terms of improvement in liver histology in patients with NAFLD. Nevertheless, the use of metformin could still be beneficial in this group as it is associated with a reduction in serum levels of lipids and glucose. (ClinicalTrials.gov number, NCT00303537).
Haukeland
John Willy
JW
Faculty Division, Department of Gastroenterology, Aker University Hospital, Trondheimsveien 235, Oslo, Norway. j.w.haukeland@medisin.uio.no
Konopski
Zbigniew
Z
Eggesbø
Heidi Beate
HB
von Volkmann
Hilde Løland
HL
Raschpichler
Gabriele
G
Bjøro
Kristian
K
Haaland
Terese
T
Løberg
Else Marit
EM
Birkeland
Kåre
K
D000284:Administration, Oral; D000328:Adult; D001706:Biopsy; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016014:Linear Models; D008111:Liver Function Tests; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin