Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions

Departments of Hepatology. Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Annals of hepatology: official journal of the Mexican Association of Hepatology (Impact Factor: 2.07). 11/2006; 6(4):222-6.
Source: PubMed


Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA- IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls).
Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 +/- 41.8 vs. 118 +/- 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 +/- 26.8 vs 74.3 +/- 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT.
Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.

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Available from: Kiran Thumburu, Dec 04, 2015
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    • "However, data about improvement in liver enzymes and hepatic histology during treatment with metformin in patients with NAFLD/NASH are controversial. Several open-label clinical studies [75–84] supported the beneficial effects on serum aminotransferases levels [75], and on IR markers [75, 76, 80–84] of NAFLD/NASH patients treated for at least 6 months with metformin (dose ranging 1.4–2.0 g/day) alone or in association with vitamin E [94] or lifestyle intervention [75, 78, 84]. "
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    • "The primary effect is thought to be the suppression of hepatic glucose production and hepatic lipogenesis [109]. Metformin activates AMPK in hepatocytes, resulting in the phosphorylation and inactivation of ACA, a rate-limiting enzyme in lipogenesis [110], and theoretically might be useful and safe in the treatment of NAFLD [111]. Surprisingly, the beneficial clinical effects seem to be limited, despite the effects of metformin on insulin resistance, most likely because long-term treatment is an absolute requirement for the prevention of progressive disease. "
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    • "hesini et al . , 2001 ) . Metformin is well tolerated in the NAFLD population , with no problem of weight gain and the only side effect being gastrointestinal intolerance . It improved aminotransferases as well as histology in patients with NASH ( Marchesini et al . , 2001 ; Nair et al . , 2004 ; Uygun et al . , 2004 ; Bugianesi et al . , 2005 and Duseja et al . , 2007 ) . Another group of drugs that is under extensive study is peroxisome proliferation - activated receptor -  agonist , commonly called " glitazones " in the context of NAFLD . Thiazolidinediones ( TZDs ) are high - affinity ligands of proliferation - activated receptor -  , which improve insulin resistance by redistributing the storag"

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