Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial

Haukeland, John Willy; Konopski, Zbigniew; Eggesbø, Heidi B.; Volkmann, Hilde Løland von; Raschpichler, Gabriele; Bjøro, Kristian; Haaland, Terese; Løberg, Else Marit; Birkeland, Kåre I.

doi:10.1080/00365520902845268

Cited by 297 publications

(267 citation statements)

References 23 publications

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“…39 Unlike other insulin sensitizers, such as thiazolidinediones, whose side effects may raise concern, the long-term safety of metformin is well established. 12,29,40 Our present findings are in agreement with results of Bugianesi et al, 18 who reported that metformin was more efficacious than dietary treatment on metabolic parameters in NAFLD patients and of Haukeland et al 41 , who found that the use of metformin was associated with weight loss and amelioration in the metabolic profile in NAFLD patients. Other studies have also found a beneficial effect of metformin on metabolic parameters, [15][16][17]41 and on liver enzymes and histology in NAFLD patients.…”

Section: Discussionsupporting

confidence: 83%

Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study

et al. 2010

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Objective: We aimed at evaluating whether the addition of low-dose metformin to dietary treatment could be an effective approach in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD). Methods: We carried out a 6-month prospective study in a series of overweight or obese patients with ultrasonographic diagnosis of hepatic steatosis. In total, 50 patients were enrolled and randomized into two groups: the first group (n ¼ 25) was given metformin (1 g per day) plus dietary treatment and the second group (n ¼ 25) was given dietary treatment alone. Results: At the end of the study, the proportion of patients with echographic evidence of fatty liver was reduced in both the metformin (Po0.0001) and the diet group (P ¼ 0.029). Moreover, patient body mass index and waist circumference significantly decreased in both groups (Po0.001). Fasting glucose, insulin resistance (evaluated as homeostasis model assessment of insulin resistance (HOMA-IR)) and serum adiponectin decreased in both groups, although these changes reached statistical significance only in the metformin group. In this group, HOMA-IR decreased from 3.3±1.6 to 2.4±1.2 (P ¼ 0.003), whereas it decreased from 3.2 ± 1.6 to 2.8 ± 1.1 (not significant, NS) in the diet group. Similarly, the proportion of patients with impaired fasting glucose declined from 35 to 5% (P ¼ 0.04) in the metformin and from 32 to 12% (NS) in the diet group. At baseline, B40% of patients in both groups met the diagnostic criteria of metabolic syndrome. This proportion decreased to 20% in the metformin group (P ¼ 0.008) and to 32% in the diet group (NS). Conclusions: In our 6-month prospective study, both low-dose metformin and dietary treatment alone ameliorated liver steatosis and metabolic derangements in patients with NAFLD. However, metformin was more effective than dietary treatment alone in normalizing several metabolic parameters in these patients.

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Section: Discussionsupporting

confidence: 83%

Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study

et al. 2010

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“…Nar and Gedik [77] reported no significant efficacy of metformin against NAFLD as assessed by US in patients with concurrent NAFLD and type 2 diabetes mellitus. Haukeland et al [78] reported a similar lack of efficacy in a larger RCT. Other studies also failed to show any major benefit of metformin on serum biochemical indices aside from improvement of arterial resistance [79].…”

Section: Metformin Cq: Are Biguanides Effective For Patients With Nafmentioning

confidence: 87%

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

et al. 2015

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Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various noninvasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary.Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 to January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.

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“…In a 48-week open-label study in 26 patients, metformin improved NASH activity in only 30% of patients, although interpretation of the study was confounded by a significant weight loss in the responders (19% lost more than 10 kilograms). 110 Haukeland et al 112 reported a similar lack of efficacy in a larger (n¼48) randomized control trial (RCT) of metformin vs. placebo with a similar dietary and exercise intervention in both groups. Other studies also failed to show major benefit for metformin on hepatic insulin sensitivity, aminotransferases [111][112][113][114][115][116] …”

Section: Metforminmentioning

confidence: 95%

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

et al. 2012

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Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial

Cited by 297 publications

References 23 publications

Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study

Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

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