Skip to main content
SpringerLink
Log in

A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity

  • Original Article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

The efficacy of pharmacological treatment in controlling childhood obesity is controversial. We aimed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification (diet and exercise).

Methods

This triple-masked randomized clinical trial was conducted among 180 participants aged 10–16 years. They were assigned randomly to 4 groups of equal number to receive metformin, fluoxetine, a combination of the two drugs, or placebo. The trial lasted for 12 weeks and participants were followed up for an additional 12-week period.

Results

Overall, 91.1% (n=164) of the enrolled participants completed the trial. After the 12-week trial, the body mass index decreased significantly in all groups receiving medications [approximately −1.2 (0.2) kg/m2, P<0.05]. This decrease was not significant in the placebo group. Waist circumference decreased significantly in the groups receiving metformin [−2.1 (0.4) cm, P=0.03)] as well as in the group receiving a combination therapy of metformin and fluoxetine [−2.5 (0.4) cm, P=0.01)]. In the 24-week follow-up study, these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine. No serious drug side-effects were reported.

Conclusions

A limited period of such treatment may help weight control, and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs. Our findings should be confirmed in future studies with a longer follow-up period.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: public-health crisis, common sense cure. Lancet 2002;360:473–482.

    Article  PubMed  Google Scholar 

  2. Kelishadi R. Childhood overweight, obesity, and the metabolic syndrome in developing countries. Epidemiol Rev 2007;29:62–76.

    Article  PubMed  Google Scholar 

  3. Kelishadi R, Ardalan G, Gheiratmand R, Gouya MM, Razaghi EM, Delavari A, et al. Association of physical activity and dietary behaviours in relation to the body mass index in a national sample of Iranian children and adolescents: CASPIAN Study. Bull World Health Organ 2007;85:19–26.

    PubMed  Google Scholar 

  4. Deckelbaum RJ, Williams CL. Childhood obesity: the health issue. Obes Res 2001;9Suppl 4:239S–243S.

    Article  PubMed  Google Scholar 

  5. Hashemipour M, Kelishadi R, Asgary S, Talaei M, Salek M, Mohammadifard N, et al. Efficacy of herbal mixtures in childhood obesity control. J Ped Neonat 2006;3:1–5

    Google Scholar 

  6. Medeiros-Neto GA. Should drug be used for treating obese children? Int J obse Relat Metab disord 1993;17:363–365.

    CAS  Google Scholar 

  7. Molnár D, Török K, Erhardt E, Jeges S. Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord 2000;24:1573–1578.

    Article  PubMed  Google Scholar 

  8. Freemark M, Bursey D. 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. Pediatrics 2001;107:E55.

    Article  CAS  PubMed  Google Scholar 

  9. Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. J Pediatr 2008;152:817–822.

    Article  CAS  PubMed  Google Scholar 

  10. Webb E, Viner R. Should metformin be prescribed to overweight adolescents in whom dietary/behavioural modifications have not helped? Arch Dis Child 2006;91:793–794.

    Article  CAS  PubMed  Google Scholar 

  11. Uli N, Sundararajan S, Cuttler L. Treatment of childhood obesity. Curr Opin Endocrinol Diabetes Obes 2008;15:37–47.

    PubMed  Google Scholar 

  12. Glueck CJ, Fontaine RN, Wang P, Subbiah MT, Weber K, Illig E, et al. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism 2001;50:856–861.

    Article  CAS  PubMed  Google Scholar 

  13. Charles MA, Eschwege E, Grandmottet P, Isnard F, Cohen JM, Bensoussan JL, et al. Treatment with metformin of non-diabetic men with hypertension, hypertriglyceridaemia and central fat distribution: the BIGPRO 1.2 trial. Diabetes Metab Res Rev 2000;16:2–7.

    Article  CAS  PubMed  Google Scholar 

  14. Lord J, Wilkin T. Metformin in polycystic ovary syndrome. Curr Opin Obstet Gynecol 2004;16:481–486.

    Article  PubMed  Google Scholar 

  15. Mannucci E, Ognibene A, Cremasco F, Bardini G, Mencucci A, Pierazzuoli E, et al. Effect of metformin on glucagonlike peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 2001;24:489–494.

    Article  CAS  PubMed  Google Scholar 

  16. Srinivasan S, Ambler GR, Baur LA, Garnett SP, Tepsa M, Yap F, et al. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. J Clin Endocrinol Metab 2006;91:2074–2080.

    Article  CAS  PubMed  Google Scholar 

  17. Fluoxetine and other drugs for treatment of obesity. Med Lett Drugs Ther 1994;36:107–108.

    Google Scholar 

  18. Halford JC, Harrold JA. Neuropharmacology of human appetite expression. Dev Disabil Res Rev 2008;14:158–164.

    Article  PubMed  Google Scholar 

  19. Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE. Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 2007;67:27–55.

    Article  CAS  PubMed  Google Scholar 

  20. Halford JC, Harrold JA, Lawton CL, Blundell JE. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr Drug Targets 2005;6:201–213.

    CAS  PubMed  Google Scholar 

  21. Dastjerdi MS, Kazemi F, Najafian A, Mohammady M, Aminorroaya A, Amini M. An open-label pilot study of the combination therapy of metformin and fluoxetine for weight reduction. Int J Obes (Lond) 2007;31:713–717.

    Google Scholar 

  22. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Adv Data 2000;314:1–27.

    PubMed  Google Scholar 

  23. Roberts CK, Chen AK, Barnard RJ. Effect of a short-term diet and exercise intervention in youth on atherosclerotic risk factors. Atherosclerosis 2007;191:98–106.

    Article  CAS  PubMed  Google Scholar 

  24. Kelishadi R, Hashemi M, Mohammadifard N, Asgary S, Khavarian N. Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children. Clin Chem 2008;54:147–153.

    Article  CAS  PubMed  Google Scholar 

  25. Kelishadi R, Ardalan G, Gheiratmand R, Majdzadeh R, Hosseini M, Gouya MM, et al. Thinness, overweight and obesity in a national sample of Iranian children and adolescents: CASPIAN Study. Child Care Health Dev 2008;34:44–54.

    CAS  PubMed  Google Scholar 

  26. Cook S, Auinger P, Li C, Ford ES. Metabolic syndrome rates in United States adolescents, from the National Health and Nutrition Examination Survey, 1999–2002. J Pediatr 2008;152:165–170.

    Article  PubMed  Google Scholar 

  27. Feinstein RA. Physical activity should be promoted at every well-child visit. AAP News 2004;24:120.

    Google Scholar 

  28. Centers for Disease Control and Prevention. http://www.cdc.gov/physicalactivity/everyone/guidelines/children.html (accessed February 24, 2009).

  29. Lucas B. Nutrition in Childhood. In: Mahan LK, Escott-Stumps, eds. Kraue’s Food, Nutrition & Diet Therapy, 10th ed. Saunders: Philadelphia, 2000: 242–245.

    Google Scholar 

  30. Atabek ME, Pirgon O. Use of metformin in obese adolescents with hyperinsulinemia: a 6-month, randomized, double-blind, placebo-controlled clinical trial. J Pediatr Endocrinol Metab 2008;21:339–348.

    CAS  PubMed  Google Scholar 

  31. Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000;85:2767–2774.

    Article  CAS  PubMed  Google Scholar 

  32. Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 2008;93:4299–4306.

    Article  CAS  PubMed  Google Scholar 

  33. Leombruni P, Pierò A, Lavagnino L, Brustolin A, Campisi S, Fassino S. A randomized, double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with Binge Eating Disorder. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1599–1605.

    Article  CAS  PubMed  Google Scholar 

  34. Guimarães C, Pereira LR, Iucif Júnior N, Cesarino EJ, de Almeida CA, de Carvalho D, et al. Tolerability and effectiveness of fluoxetine, metformin and sibutramine in reducing anthropometric and metabolic parameters in obese patients. Arq Bras Endocrinol Metabol 2006;50:1020–1025.

    PubMed  Google Scholar 

  35. Marcus C. Pharmacological Treatment of Childhood Obesity. In: Kiess W, Marcus C, Wabitsch M, eds. Obesity in Childhood and Adolescence. Pediatr Adolesc Med, Basel: Karger, 2004: 211–228.

    Chapter  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Isfahan Endocrine & Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Hasan Rezvanian & Mahin Hashemipour

  2. Pediatric Preventive Cardiology Department, Isfahan Cardiovascular Research Center, Isfahan, Iran

    Roya Kelishadi

  3. Isfahan Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

    Naser Tavakoli

  4. Environmental Engineering, Science & Research University, Tehran, Iran

    Parinaz Poursafa

  5. Isfahan Cardiovascular Research Centre, Isfahan University of Medical Sciences, PO. Box 81465-1148, Isfahan, Iran

    Roya Kelishadi

Authors
  1. Hasan Rezvanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahin Hashemipour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roya Kelishadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naser Tavakoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Parinaz Poursafa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roya Kelishadi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rezvanian, H., Hashemipour, M., Kelishadi, R. et al. A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity. World J Pediatr 6, 317–322 (2010). https://doi.org/10.1007/s12519-010-0232-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-010-0232-x

Key words

Search

Navigation