Long-term metformin treatment in adolescents with obesity and insulin resistance, results of an open label extension study

Background/Objectives Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-con...

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Published inNutrition & diabetes Vol. 8; no. 1; pp. 47 - 10
Main Authors Lentferink, Y. E., van der Aa, M. P., van Mill, E. G. A. H., Knibbe, C. A. J., van der Vorst, M. M. J.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 10.09.2018
Nature Publishing Group
Subjects
692/699/2743/393
692/700/1720
692/700/2817
Adolescent
Antidiabetics
Body Mass Index
Child
Clinical Nutrition
Diabetes
Epidemiology
Female
Humans
Hypoglycemic Agents - therapeutic use
Insulin resistance
Insulin Resistance - physiology
Internal Medicine
Male
Medicine
Medicine & Public Health
Metabolic Diseases
Metformin - therapeutic use
Obesity
Off-Label Use
Pediatric Obesity - drug therapy
Pediatric Obesity - metabolism
Teenagers
Treatment Outcome
Online AccessGet full text
ISSN2044-4052
2044-4052
DOI10.1038/s41387-018-0057-6

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Abstract Background/Objectives Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed. Subjects/Methods After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR. Results Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 – 17.9), BMI 31.2 (22.3 – 45.1), HOMA-IR 3.4 (0.2 – 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (−2.1 to +5.1)). For HOMA-IR, a decrease was observed (−1.1 (−4.6 to +1.4)). Conclusion While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
AbstractList Background/Objectives Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed. Subjects/Methods After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR. Results Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 – 17.9), BMI 31.2 (22.3 – 45.1), HOMA-IR 3.4 (0.2 – 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (−2.1 to +5.1)). For HOMA-IR, a decrease was observed (−1.1 (−4.6 to +1.4)). Conclusion While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed.BACKGROUND/OBJECTIVESOff-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed.After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR.SUBJECTS/METHODSAfter completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR.Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)).RESULTSOverall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)).While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.CONCLUSIONWhile metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
Background/ObjectivesOff-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed.Subjects/MethodsAfter completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR.ResultsOverall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 – 17.9), BMI 31.2 (22.3 – 45.1), HOMA-IR 3.4 (0.2 – 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (−2.1 to +5.1)). For HOMA-IR, a decrease was observed (−1.1 (−4.6 to +1.4)).ConclusionWhile metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed. After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR. Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)). While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
ArticleNumber 47
Author van Mill, E. G. A. H.
van der Vorst, M. M. J.
van der Aa, M. P.
Knibbe, C. A. J.
Lentferink, Y. E.
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CastroAVKolkaCMKimSPBergmanRNObesity, insulin resistance and comorbidities? Mechanisms of associationArq. Bras. Endocrinol. Metabol.20145860060910.1590/0004-2730000003223252114424423826
van der AaMPLong-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trialNutr. Diabetes20166e22810.1038/nutd.2016.372757124950221491:CAS:528:DC%2BC28XhsVSrsLzM
van der AaMPKnibbeCABoerAvan der VorstMMDefinition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensusJ. Pediatr. Endocrinol. Metab.20173012313127984205
MoranAInsulin resistance during puberty: results from clamp studies in 357 childrenDiabetes1999482039204410.2337/diabetes.48.10.2039105123711:CAS:528:DyaK1MXmsVCjs7Y%3D
YanovskiJAEffects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trialDiabetes20116047748510.2337/db10-11852122831030283471:CAS:528:DC%2BC3MXisVOmur0%3D
van der AaMPElstMAvan MilEGKnibbeCAvan der VorstMMMETFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents—study protocol of a randomized controlled studyTrials2014152076215-15-20710.1186/1745-6215-15-2072489913740533051:CAS:528:DC%2BC2cXhs1ynsb%2FE
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ClarsonCLEffects of a comprehensive, intensive lifestyle intervention combined with metformin extended release in obese adolescentsInt. Sch. Res. Not.20142014659410
Diabetes Prevention Program Research Group.Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes StudyDiabetes Care20123573173710.2337/dc11-12991:CAS:528:DC%2BC38Xmt1Chs78%3D
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IngeTHWeight loss and health status 3 years after bariatric surgery in adolescentsNew Engl. J. Med.201637411312310.1056/NEJMoa1506699265447251:CAS:528:DC%2BC28XhtV2mur%2FM
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MatthewsDRHomeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in manDiabetologia19852841241910.1007/BF0028088338998251:CAS:528:DyaL2MXlslKnu7k%3D
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Snippet Background/Objectives Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin...
Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents...
Background/ObjectivesOff-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 47
SubjectTerms 692/699/2743/393
692/700/1720
692/700/2817
Adolescent
Antidiabetics
Body Mass Index
Child
Clinical Nutrition
Diabetes
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Humans
Hypoglycemic Agents - therapeutic use
Insulin resistance
Insulin Resistance - physiology
Internal Medicine
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Medicine
Medicine & Public Health
Metabolic Diseases
Metformin - therapeutic use
Obesity
Off-Label Use
Pediatric Obesity - drug therapy
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Title Long-term metformin treatment in adolescents with obesity and insulin resistance, results of an open label extension study
URI https://link.springer.com/article/10.1038/s41387-018-0057-6
https://www.ncbi.nlm.nih.gov/pubmed/30197416
https://www.proquest.com/docview/2101262177
https://www.proquest.com/docview/2101921090
https://pubmed.ncbi.nlm.nih.gov/PMC6129504
Volume 8
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