Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin.
OBJECTIVE
In a previous study we showed that metformin reduced BMI z-scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines.


METHODS
The 6-month trial was randomized, double blinded and placebo controlled; a total of 14 metformin-treated (500 mg bid) and 15 placebo-treated subjects completed the study. There were no dietary restrictions.


RESULTS
In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo-treated subjects at the 3 to 5 month time-points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 muU/mL (p < 0.05).


CONCLUSIONS
Our findings suggest that metformin might reduce the rates or severity of liver dysfunction in selected high-risk adolescents.
Freemark
Michael
M
Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, North Carolina 27710, USA. freem001@mc.duke.edu
D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D003124:Colorimetry; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology* / Q000208:ethnology; D004311:Double-Blind Method; D005006:Ethnicity / Q000706:statistics & numerical data; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy* / Q000453:epidemiology* / Q000208:ethnology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D008107:Liver Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology*; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use*; D009765:Obesity / Q000453:epidemiology* / Q000208:ethnology; D017678:Sex Distribution
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin