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Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study.
Clin Ther. 2008 Jun; 30(6):1168-76.CT

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<or=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<or=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.

Authors+Show Affiliations

Liver Unit, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

18640473

Citation

Nobili, Valerio, et al. "Metformin Use in Children With Nonalcoholic Fatty Liver Disease: an Open-label, 24-month, Observational Pilot Study." Clinical Therapeutics, vol. 30, no. 6, 2008, pp. 1168-76.
Nobili V, Manco M, Ciampalini P, et al. Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. Clin Ther. 2008;30(6):1168-76.
Nobili, V., Manco, M., Ciampalini, P., Alisi, A., Devito, R., Bugianesi, E., Marcellini, M., & Marchesini, G. (2008). Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. Clinical Therapeutics, 30(6), 1168-76. https://doi.org/10.1016/j.clinthera.2008.06.012
Nobili V, et al. Metformin Use in Children With Nonalcoholic Fatty Liver Disease: an Open-label, 24-month, Observational Pilot Study. Clin Ther. 2008;30(6):1168-76. PubMed PMID: 18640473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. AU - Nobili,Valerio, AU - Manco,Melania, AU - Ciampalini,Paolo, AU - Alisi,Anna, AU - Devito,Rita, AU - Bugianesi,Elisabetta, AU - Marcellini,Matilde, AU - Marchesini,Giulio, PY - 2008/04/11/accepted PY - 2008/7/22/pubmed PY - 2008/12/17/medline PY - 2008/7/22/entrez SP - 1168 EP - 76 JF - Clinical therapeutics JO - Clin Ther VL - 30 IS - 6 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<or=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<or=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. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/18640473/Metformin_use_in_children_with_nonalcoholic_fatty_liver_disease:_an_open_label_24_month_observational_pilot_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(08)00213-0 DB - PRIME DP - Unbound Medicine ER -