Metformin use in children with nonalcoholic fatty liver disease: An open-label, 24-month, observational pilot study

Valerio Nobili, Melania Manco, Paolo Ciampalini, Anna Alisi, Rita Devito, Elisabetta Bugianesi, Matilde Marcellini, Giulio Marchesini

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Abstract

Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21-43] to 32 [20-46] U/L; control: 66 [28-121] to 33 [14-45] U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5-5.11] to 1.3 [0.13-4.21]; control: 2.29 [0.86-5.76] to 1.5 [0.70-4.23]; P ≤ 0.01). Steatosis was reduced in both the MET (P = 0.02) and control (P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group (P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.

Original languageEnglish
Pages (from-to)1168-1176
Number of pages9
JournalClinical Therapeutics
Volume30
Issue number6
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Metformin
Observational Studies
Life Style
Histology
Liver
Insulin Resistance
Homeostasis
Body Weight
Biopsy
Control Groups
Non-alcoholic Fatty Liver Disease
Fatty Liver
Enzymes
Transaminases
Alanine Transaminase
Counseling
Consensus
Fibrosis
Antioxidants
Exercise

Keywords

  • insulin resistance
  • metformin
  • nonalcoholic fatty liver disease
  • nonalcoholic steatohepatitis
  • weight loss

ASJC Scopus subject areas

  • Pharmacology

Cite this

Metformin use in children with nonalcoholic fatty liver disease : An open-label, 24-month, observational pilot study. / Nobili, Valerio; Manco, Melania; Ciampalini, Paolo; Alisi, Anna; Devito, Rita; Bugianesi, Elisabetta; Marcellini, Matilde; Marchesini, Giulio.

In: Clinical Therapeutics, Vol. 30, No. 6, 06.2008, p. 1168-1176.

Research output: Contribution to journalArticle

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abstract = "Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21-43] to 32 [20-46] U/L; control: 66 [28-121] to 33 [14-45] U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5-5.11] to 1.3 [0.13-4.21]; control: 2.29 [0.86-5.76] to 1.5 [0.70-4.23]; P ≤ 0.01). Steatosis was reduced in both the MET (P = 0.02) and control (P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group (P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.",
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AU - Nobili, Valerio

AU - Manco, Melania

AU - Ciampalini, Paolo

AU - Alisi, Anna

AU - Devito, Rita

AU - Bugianesi, Elisabetta

AU - Marcellini, Matilde

AU - Marchesini, Giulio

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N2 - Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21-43] to 32 [20-46] U/L; control: 66 [28-121] to 33 [14-45] U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5-5.11] to 1.3 [0.13-4.21]; control: 2.29 [0.86-5.76] to 1.5 [0.70-4.23]; P ≤ 0.01). Steatosis was reduced in both the MET (P = 0.02) and control (P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group (P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.

AB - Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21-43] to 32 [20-46] U/L; control: 66 [28-121] to 33 [14-45] U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5-5.11] to 1.3 [0.13-4.21]; control: 2.29 [0.86-5.76] to 1.5 [0.70-4.23]; P ≤ 0.01). Steatosis was reduced in both the MET (P = 0.02) and control (P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group (P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.

KW - insulin resistance

KW - metformin

KW - nonalcoholic fatty liver disease

KW - nonalcoholic steatohepatitis

KW - weight loss

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