The Effects of Metformin on Body Mass Index and Glucose Tolerance  in Obese Adolescents With Fasting Hyperinsulinemia and a  Family History of Type 2 Diabetes

Freemark, Michael; Bursey, Deborah

doi:10.1542/peds.107.4.e55

Cited by 388 publications

(348 citation statements)

References 65 publications

(69 reference statements)

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“…Metformin was compared with placebo in 29 obese adolescents (mean BMI 40 kg/m 2 ) over a treatment period of 6 months. 98 Mean BMI decreased by 0.5 kg/m 2 in the metformin group and increased by 0.23 kg/m 2 in the placebo group (Po0.02). These data are broadly similar to those from adults, described above, although further studies are required for a definitive assessment of the effect of metformin on body weight in this population.…”

Section: Pediatric Obesitymentioning

confidence: 90%

Metformin and body weight

2007

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Most patients with type 2 diabetes are overweight or obese, overweight or obesity increases the risk of developing type 2 diabetes and obesity per se is strongly associated with multiple cardiometabolic risk factors. However, many antidiabetic treatments increase body weight. The oral antidiabetic agent, metformin, has been evaluated in hundreds of clinical studies in diverse patient populations during approximately five decades of clinical use. This review summarizes the effects of metformin on body weight, with special reference to studies of longer duration (X6 months) as both diabetes and obesity are long-term conditions. Approximately half of studies in drug-naive type 2 diabetic patients demonstrated significant weight loss with metformin compared with baseline or comparator drugs, although pooled analyses have suggested no significant effect versus placebo. Similarly, metformin has been shown to induce weight loss in obese nondiabetic populations, although studies of long duration in this population are scarce. Metformin does appear to mitigate the adverse effects of insulin on body weight. The weight-neutral or weight-sparing effects of metformin constitute a therapeutic advantage in diabetes management where other first-line oral antidiabetic treatments often promote clinically significant weight gain.

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Section: Pediatric Obesitymentioning

confidence: 90%

Metformin and body weight

2007

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“…81 Metformin is also effective in reducing the incidence of diabetes in those at high risk 80 and has been used with some success in management of symptoms of PCOS in adolescents. [82][83][84] However there is a lack of large, randomized controlled trials to assess efficacy of symptom control in adolescents and no prospective study, even in adults, to examine the long-term effects of metformin in prevention or reduction of metabolic complications of PCOS. Recently, an impressively large and well-conducted trial of metformin as an adjunct to clomiphene treatment for induction of ovulation has shown no benefit of metformin.…”

Section: Management Of Pcos In Adolescentsmentioning

confidence: 99%

Polycystic ovary syndrome in adolescents

2008

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Background: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women and typically presents during adolescence. The clinical and biochemical presentation is heterogeneous, but elevated serum concentrations of androgens are the most consistent biochemical abnormality and may be considered to be the hallmark of the syndrome. Many women with PCOS also have insulin resistance and hyperinsulinaemia, which may contribute to the clinical and endocrine abnormalities. The aetiology of PCOS is not clear but studies in the Rhesus monkey suggest that exposure to excess androgen during intrauterine life results in many of the features of human PCOS, including ovarian dysfunction, abnormal LH secretion and insulin resistance. Objective: To review the studies from the literature, including those of the author, regarding aetiology, presentation and management of PCOS in adolescents. Results and conclusions: We have proposed that PCOS in adolescents arises as a result of a genetically determined disorder of ovarian function that results in hyper-secretion of androgens, possibly during fetal life and also during physiological activation of the hypothalamic-pituitary-ovarian in infancy and at the onset of puberty. There is plentiful evidence for a genetic basis for PCOS (it appears to be a complex endocrine disorder resulting from the effects of a several genes), but environmental factors, notably nutrition, influence the clinical and biochemical phenotype. Obesity unmasks or amplifies symptoms, endocrine and metabolic abnormalities. The increasing incidence of childhood obesity has resulted in an alarming Increase not only in distressing symptoms but also impaired glucose tolerance and even diabetes among adolescent girls with PCOS. The search for PCOS genes in this condition, that is not only heterogeneous but also presents only in women of reproductive age, is not straightforward and has produced few convincing candidates so far. In due course, however, identification of the major susceptibility loci is likely to provide key insight into the aetiology of the syndrome and improve diagnosis and management.

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“…Metformin, an insulin sensitizer, is administered to children with T2DM, but in some trials, it reduced BMI zscore even in the absence of dietary intervention. 26 Bariatric surgery may be indicated in selected subjects with extreme obesity and severe comorbidities. 27 Potential candidates for this type of treatment should be referred to centres with multidisciplinary weight management teams.…”

Section: Treatmentmentioning

confidence: 99%