Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538509
Title: Metformin in obese children and adolescents : the MOCA Trial
Author: Kendall, Deborah
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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Abstract:
Background and objective: Childhood obesity is a serious global health problem and it is associated with insulin resistance and significantly increased risk for development of type 2 diabetes and cardiovascular disease. Metformin reduces the risk of developing T2D in adult patients with obesity and insulin resistance. However there is limited and inconclusive data in obese non diabetic children and adolescents. The objective of the Metformin in Obese Children and Adolescents (MOCA trial) was to assess the effect of metformin on body composition, metabolic risk factors and adipokines. Design and methods: The MOCA trial was a six month multi-centre randomized, double-blind placebo-controlled trial of metformin (1.5g daily) in children and adolescents (8-18 years) with insulin resistance and/or impaired glucose tolerance. Auxology, blood pressure measurement and fasting blood tests (insulin, glucose, fasting lipids, ALT, bilirubin, CRP, lactate, resistin, adiponectin, leptin) were performed at baseline, three and six months. A prolonged oral glucose tolerance test was performed at baseline and after six months. Measures of insulin resistance/sensitivity were calculated including HOMA-IR and the adiponectin: leptin (A/L) ratio. Results: 151 obese children participated in the trial (metformin:77, placebo:78). 102 (67.5%) female, 99 (65.6%) post-pubertal, 115 (76.2%) White British and 36 (23.8%) British Asian or Afro-Caribbean. Mean age of participants was 13.7 ±2.3 year and mean BMI-SDS 3.4 (0.5). In regression analysis, controlling for baseline values, sex, ethnicity and pubertal status, metformin had a greater treatment effect over placebo for BMI at three months, that was sustained at six months (-0.25 kg/m2, p=0.01, 95% CI 0.29 to 1.86) and BMI-SDS (-0.1, p=0.01, 95% CI 0.02 to 0.19). Fasting glucose reduced (-0.03 mmol/l, p=0.03) and A/L ratio increased at three months (+0.04, p=0.03), but the improvements were lost at six months. The other measures of insulin sensitivity, metabolic risk factors and concentrations of adipokines did not change with metformin treatment. Conclusions: Metformin therapy for obese children with abnormal insulin glucose status is safe, well tolerated and has a small beneficial treatment effect over placebo for BMI, BMI-SDS, fasting glucose and A/L ratio at three months, with the changes in body composition sustained at six months. A three month course of metformin should be considered by Paediatricians to halt the inexorable rise in BMI-SDS in these children, improve insulin glucose status and act as catalyst and support for more radical change in lifestyle in the individual. Trial register number: ISRCTN 19517475.
Supervisor: Clayton, Peter Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.538509  DOI: Not available
Keywords: Childhood Obesity ; Insulin Resistance ; Metformin
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