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Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial

BACKGROUND: As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resista...

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Autores principales: van der Aa, M P, Elst, M A J, van de Garde, E M W, van Mil, E G A H, Knibbe, C A J, van der Vorst, M M J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022149/
https://www.ncbi.nlm.nih.gov/pubmed/27571249
http://dx.doi.org/10.1038/nutd.2016.37
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author van der Aa, M P
Elst, M A J
van de Garde, E M W
van Mil, E G A H
Knibbe, C A J
van der Vorst, M M J
author_facet van der Aa, M P
Elst, M A J
van de Garde, E M W
van Mil, E G A H
Knibbe, C A J
van der Vorst, M M J
author_sort van der Aa, M P
collection PubMed
description BACKGROUND: As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied. METHODS: In a randomized placebo-controlled double-blinded trial, 62 adolescents with obesity aged 10–16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months. Primary end points were change in body mass index (BMI) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Secondary end points were safety and tolerability of metformin. Other end points were body fat percentage and HbA1c. RESULTS: Forty-two participants completed the 18-month study (66% girls, median age 13 (12–15) years, BMI 30.0 (28.3 to 35.0) kg m(−2) and HOMA-IR 4.08 (2.40 to 5.88)). Median ΔBMI was +0.2 (−2.9 to 1.3) kg m(−2) (metformin) versus +1.2 (−0.3 to 2.4) kg m(−2) (placebo) (P=0.015). No significant difference was observed for HOMA-IR. No serious adverse events were reported. Median change in fat percentage was −3.1 (−4.8 to 0.3) versus −0.8 (−3.2 to 1.6)% (P=0.150), in fat mass −0.2 (−5.2 to 2.1) versus +2.0 (1.2–6.4) kg (P=0.007), in fat-free mass +2.0 (−0.1 to 4.0) versus +4.5 (1.3 to 11.6) kg (P=0.047) and in ΔHbA1c +1.0 (−1.0 to 2.3) versus +3.0 (0.0 to 5.0) mmol mol(−1) (P=0.020) (metformin versus placebo). CONCLUSIONS: Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo. Therefore, metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance.
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spelling pubmed-50221492016-09-20 Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial van der Aa, M P Elst, M A J van de Garde, E M W van Mil, E G A H Knibbe, C A J van der Vorst, M M J Nutr Diabetes Original Article BACKGROUND: As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied. METHODS: In a randomized placebo-controlled double-blinded trial, 62 adolescents with obesity aged 10–16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months. Primary end points were change in body mass index (BMI) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Secondary end points were safety and tolerability of metformin. Other end points were body fat percentage and HbA1c. RESULTS: Forty-two participants completed the 18-month study (66% girls, median age 13 (12–15) years, BMI 30.0 (28.3 to 35.0) kg m(−2) and HOMA-IR 4.08 (2.40 to 5.88)). Median ΔBMI was +0.2 (−2.9 to 1.3) kg m(−2) (metformin) versus +1.2 (−0.3 to 2.4) kg m(−2) (placebo) (P=0.015). No significant difference was observed for HOMA-IR. No serious adverse events were reported. Median change in fat percentage was −3.1 (−4.8 to 0.3) versus −0.8 (−3.2 to 1.6)% (P=0.150), in fat mass −0.2 (−5.2 to 2.1) versus +2.0 (1.2–6.4) kg (P=0.007), in fat-free mass +2.0 (−0.1 to 4.0) versus +4.5 (1.3 to 11.6) kg (P=0.047) and in ΔHbA1c +1.0 (−1.0 to 2.3) versus +3.0 (0.0 to 5.0) mmol mol(−1) (P=0.020) (metformin versus placebo). CONCLUSIONS: Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo. Therefore, metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance. Nature Publishing Group 2016-08 2016-08-29 /pmc/articles/PMC5022149/ /pubmed/27571249 http://dx.doi.org/10.1038/nutd.2016.37 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
van der Aa, M P
Elst, M A J
van de Garde, E M W
van Mil, E G A H
Knibbe, C A J
van der Vorst, M M J
Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
title Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
title_full Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
title_fullStr Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
title_full_unstemmed Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
title_short Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
title_sort long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022149/
https://www.ncbi.nlm.nih.gov/pubmed/27571249
http://dx.doi.org/10.1038/nutd.2016.37
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