Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study

Abstract

Objective: To study whether metformin reduces obesity, homeostasis model assessment for insulin resistance index (HOMA-IR), and the metabolic syndrome (MtS) in obese European adolescents in addition to previous unsuccessful lifestyle intervention. Design and methods: After 6 months of multiprofessional lifestyle intervention, 70 out of 86 adolescents without improvement in body mass index (BMI) and HOMA-IR were randomized into either the placebo (nZ34) or the metformin group (2!500 mg/day, nZ36) in addition to ongoing lifestyle intervention for another 6 months. Results: Age was 13.8 years, BMI was 33.1 kg/m 2 , 65% were female, and 89% were Caucasians. During lifestyle intervention alone, BMI and HOMA-IR deteriorated significantly. In the subsequent medication period, HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups (HOMA-IR decreased 73 vs 54% respectively in metformin versus placebo; PZ0.048), but BMI remained unchanged. The insulin sensitivity index, however, only improved in the metformin group. High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication. MtS remained unchanged. Conclusions: Obese European adolescents' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention. Most differences did not reach statistical significance, probably due to improved compliance with lifestyle intervention as a placebo effect. In addition, the metformin dose may be too low.

Assessing and treating insulin resistance in women with polycystic ovarian syndrome

“…PCOS women randomized to both metformin and lifestyle interventions (compared to placebo) showed improvements in HOMA IR after 4 mo [106] . In European adolescents with PCOS who failed to achieve improvements in HOMAIR after 6 mo of lifestyle intervention, both metformin and placebo reduced IR over 6 mo, although metformin offered no benefit over placebo [107] . Lifestyle modification in ado lescents has been successful in reducing hyperandroge nism [103] .…”

Systematic Review of Metformin Use in Obese Nondiabetic Children and Adolescents

“…Fourteen trials were identified [15,16,17,18,19,20,21,22,23,24,25,26,27,28]. However, 3 studies [16,20,23] were excluded for their short duration (<6 months).…”

“…Thus, 11 trials were selected for inclusion in this review. All the trials included are double-blind randomized placebo-controlled studies [15,17,18,19,22,24,25,28], except 3 [21,26,27] which are not placebo controlled. In those studies, the metformin group (metformin plus lifestyle intervention) was compared with a lifestyle intervention alone group (placebo was not administered).…”

Type 2 diabetes mellitus in children and adolescents

“…Recent intervention studies have convincingly demonstrated that adoption of a healthy lifestyle characterized by healthy eating, regular physical activity and subsequent modest weight loss can prevent the progression of impaired glucose tolerance to clinical diabetes mellitus [76] . However, the use metformin was not effective to prevent type 2 diabetes mellitus in obese adolescents with impaired glucose tolerance [77] . This might be attributed to the fact, that impaired glucose tolerance normalized physiologically at the end of puberty even without intervention [20] .…”