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The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension

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Abstract

Objective

Topiramate (TPM) has been reported to reduce body weight beyond a placebo in the treatment of obese participants, but the effect of this agent on components of energy balance has not yet been established in humans. Thus, the aim of this study was to study the impact of TPM on food preferences, measures of satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure.

Methods

The study design consisted of a 6-month, single-center, randomized, double-blind, parallel group, placebo-controlled trial with a 6-month open-label extension. The study included 68 sedentary men with abdominal obesity (waist circumference ≥100 cm), of between 25 and 55 years of age, with a dyslipidemic profile and a body mass index (BMI) ≥27 and ≤40 kg/m2.

Results

Treatment with TPM produced significant changes in anthropometric variables and body composition compared with placebo. However, at the end of the 1-year study, the placebo/TPM group showed similar weight loss and reduction in body fatness compared with the TPM/TPM group. For instance, at the end of the 12-month intervention, mean percentage of body weight loss from baseline was about −5% in both groups (−4 kg fat loss). Topiramate treatment reduced energy intake, be it in the context of an ad libitum buffet-type meal or under free living conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body indirect calorimetry adjusted for body weight and age was not altered by TPM treatment.

Conclusion

Topiramate treatment produced significantly greater weight loss than placebo and the majority of this loss was explained by a decrease in body fat stores. Most of the weight loss effect produced by TPM therapy was observed within a period of 6 months. Finally, TPM treatment had an impact on energy balance through a reduction in food intake that appears to have created an energy deficit of about 30,000–40,000 kcal compared with treatment with the placebo over 6 months.

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References

  1. Bray GA, Blackburn GL, Ferguson JM, Greenway FL, Jain AK, Mendel CM, Mendels J, Ryan DH, Schwartz SL, Scheinbaum ML, Seaton TB (1999) Sibutramine produces dose-related weight loss. Obes Res 7:189–198

    PubMed  CAS  Google Scholar 

  2. Sjostrom L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HP, Krempf M (1998) Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 352:167–172

    Article  PubMed  CAS  Google Scholar 

  3. Picard F, Deshaies Y, Lalonde J, Samson P, Richard D (2000) Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats. Obes Res 8:656–663

    PubMed  CAS  Google Scholar 

  4. York DA, Singer L, Thomas S, Bray GA (2000) Effect of topiramate on body weight and body composition of Osborne-Mendel rats fed a high-fat diet: alterations in hormones, neuropeptide, and uncoupling-protein mRNAs. Nutrition 16:967–975

    Article  PubMed  CAS  Google Scholar 

  5. Richard D, Picard F, Lemieux C, Lalonde J, Samson P, Deshaies Y (2002) The effects of topiramate and sex hormones on energy balance of male and female rats. Int J Obes Relat Metab Disord 26:344–353

    Article  PubMed  CAS  Google Scholar 

  6. Richard D, Ferland J, Lalonde J, Samson P, Deshaies Y (2000) Influence of topiramate in the regulation of energy balance. Nutrition 16:961–966

    Article  PubMed  CAS  Google Scholar 

  7. Bray GA, Hollander P, Klein S, Kushner R, Levy B, Fitchet M, Perry BH, U.S. Topiramate Research Group (2003) A 6-month randomized, placebo-controlled, dose-ranging trial for weight loss in obesity. Obes Res 11:722–733

    PubMed  CAS  Google Scholar 

  8. Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M, for the OBES-002 Study Group (2004) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes Relat Metab Disord 28:1399–1410

    Article  PubMed  CAS  Google Scholar 

  9. Astrup A, Caterson I, Zelissen P, Guy-Grand B, Carruba M, Levy B, Sun X, Fitchet M, OBES-004 Study Group (2004) Topiramate: long-term maintenance of weight loss induced by low-calorie diet in obese subjects. Obes Res 12:1658–1669

    Article  PubMed  CAS  Google Scholar 

  10. Airlie (VA) Consensus Conference (1988) Standardization of anthropometric measurements. Human Kinetics Publishers, Champaign, IL

    Google Scholar 

  11. Lohman TG (1988) Anthropometry and body composition. In: Lohman TG, Roche AF, Martorell R (eds) Anthropometric standardization reference manual. Human Kinetics, Champaign, IL

    Google Scholar 

  12. Behnke AR, Wilmore JH (1974) Evaluation and regulation of body build and composition. In: Behnke AR (eds) Evaluation and regulation of body build and composition. Englewood Cliffs, Prentice-Hall, NJ, pp 20–37

    Google Scholar 

  13. Meneely GR, Kaltreider NL (1949) Volume of the lung determined by helium dilution. J Clin Invest 28:129–139

    PubMed  CAS  Google Scholar 

  14. Siri WE (1956) The gross composition of the body. Adv Biol Med Phys 4:239–280

    PubMed  CAS  Google Scholar 

  15. Hill AJ, Blundell JE (1986) The effects of a high-protein or high-carbohydrate meal on subjective motivation to eat and food preferences. Nutr Behav 3:133–144

    Google Scholar 

  16. Doucet E, Imbeault P, St-Pierre S, Alméras N, Mauriège P, Richard D, Tremblay A (2000) Appetite after weight loss by energy restriction and low-fat diet-exercise follow-up. Int J Obes 24:906–914

    Article  CAS  Google Scholar 

  17. Arvaniti K, Richard D, Tremblay A (2000) Reproducibility of energy and macronutrient intake and related substrate oxidation rates in a buffet-type meal. Br J Nutr 83:489–495

    PubMed  CAS  Google Scholar 

  18. Canadian Nutrient File (2005) Health and Welfare, Canada

  19. Tremblay A, Sévigny J, Leblanc C, Bouchard C (1983) The reproducibility of a three-day dietary record. Nutr Res 3:819–830

    Article  Google Scholar 

  20. Weir JB (1949) New method for calculating metabolic rate with special references to protein metabolism. J Physiol 109:1–9

    PubMed  Google Scholar 

  21. Bouchard C (1985) Body-composition assessments in youth and adults. In: Roche E Jr (eds) Report of the Sixth ROSS Conference on Medical Research. Ross Laboratories, Colombus, OH

    Google Scholar 

  22. Frayn K (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 55:628–634

    PubMed  CAS  Google Scholar 

  23. White MD, Buemann B, Alméras N, Després JP, Bouchard C, Tremblay A (1996) Reproducibility of 24-h energy expenditure and macronutrient oxidation rates in a indirect calorimeter. J Appl Physiol 80:133–139

    PubMed  CAS  Google Scholar 

  24. White MD, Bouchard G, Buemann B, Alméras N, Després JP, Bouchard C, Tremblay A (1997) Energy and macronutrient balances for humans in a whole body metabolic chamber without control of preceding diet and activity level. Int J Obesity 21:135–140

    Article  CAS  Google Scholar 

  25. Tremblay A, Poehlman ET, Després JP, Thériault G, Danforth E, Bouchard C (1997) Endurance training with constant energy intake in identical twins: changes over time in energy expenditure and related hormones. Metabolism 46:499–503

    Article  PubMed  CAS  Google Scholar 

  26. Prud’homme D, Dumont M, Brochu M, Alméras N, Nadeau A, Després JP (1997) Beneficial effects of a 12-week fenfluramine treatment on the cardiovascular disease risk profile of visceral obese men. Int J Obes 21[Suppl 2]:S-65

    Google Scholar 

  27. Hins J, Sériès F, Alméras N, Tremblay A (2006) Relationship between severity of nocturnal desaturation and adaptative thermogenesis: preliminary data of apneic patients tested in a whole-body indirect calorimetry chamber. Int J Obes 30:574–577

    Article  CAS  Google Scholar 

  28. Doucet E, Imbeault P, St-Pierre S, Almeras N, Mauriège P, Després JP, Bouchard C, Tremblay A (2003) Greater than predicted decrease in energy expenditure during exercise after body weight loss in obese men. Clin Sci (Lond) 105:89–95

    Article  Google Scholar 

  29. Leibel RL, Rosenbaum M, Hirsch J (1995) Changes in energy expenditure resulting from altered body weight. N Engl J Med 332:621–628

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was funded by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

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Correspondence to Angelo Tremblay.

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Tremblay, A., Chaput, JP., Bérubé-Parent, S. et al. The effect of topiramate on energy balance in obese men: a 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension. Eur J Clin Pharmacol 63, 123–134 (2007). https://doi.org/10.1007/s00228-006-0220-1

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  • DOI: https://doi.org/10.1007/s00228-006-0220-1

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