Abstract OBJECTIVES Metformin proved useful in the treatment of non-alcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin vs. prescriptive diet or vitamin E. METHODS In an open label, randomized trial, non-diabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12-months. The control cases were given either given vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology. RESULTS: Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (P < 0.0001), and alanine aminotransferase normalized in 56% of cases (Odds Ratio vs. Controls, 3.11; 95% Confidence Interval, 1.56 – 6.20; P = 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases and change in BMI (OR, 5.98; 95% CI, 2.05 – 17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (P = 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 non-responders) showed a significant decrease in liver fat (P = 0.0004), necroinflammation and fibrosis (P = 0.012 for both). No side effects were observed during metformin treatment. CONCLUSIONS: Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.
A randomized controlled trial of metformin vs. vitamin E or prescriptive diet in non-alcoholic fatty liver disease / E Bugianesi; E Gentilcore; R Manini; S Natale; E Vanni; N Villanova; E David; M Rizzetto; G Marchesini Reggiani. - In: THE AMERICAN JOURNAL OF GASTROENTEROLOGY. - ISSN 0002-9270. - STAMPA. - 100:(2005), pp. 182-190. [10.1111/j.1572-0241.2005.41583.x]
A randomized controlled trial of metformin vs. vitamin E or prescriptive diet in non-alcoholic fatty liver disease
VILLANOVA, NICOLA;MARCHESINI REGGIANI, GIULIO
2005
Abstract
Abstract OBJECTIVES Metformin proved useful in the treatment of non-alcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin vs. prescriptive diet or vitamin E. METHODS In an open label, randomized trial, non-diabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12-months. The control cases were given either given vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology. RESULTS: Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (P < 0.0001), and alanine aminotransferase normalized in 56% of cases (Odds Ratio vs. Controls, 3.11; 95% Confidence Interval, 1.56 – 6.20; P = 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases and change in BMI (OR, 5.98; 95% CI, 2.05 – 17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (P = 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 non-responders) showed a significant decrease in liver fat (P = 0.0004), necroinflammation and fibrosis (P = 0.012 for both). No side effects were observed during metformin treatment. CONCLUSIONS: Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
