Pharmacological management of appetite expression in obesity

Nature Reviews Endocrinology volume 6, pages255–269(2010)Cite this article

Subjects

Abstract

For obese individuals, successful weight loss and maintenance are notoriously difficult. Traditional drug development fails to exploit knowledge of the psychological factors that crucially influence appetite, concentrating instead on restrictive criteria of intake and weight reduction, allied to a mechanistic view of energy regulation. Drugs are under development that may produce beneficial changes in appetite expression in the obese. These currently include glucagon-like peptide-1 analogs such as liraglutide, an amylin analog davalintide, the 5-HT2C receptor agonist lorcaserin, the monoamine re-uptake inhibitor tesofensine, and a number of combination therapies such as pramlintide and metreleptin, bupropion and naltrexone, phentermine and topiramate, and bupropion and zonisamide. However, the effects of these treatments on eating behavior remain poorly characterized. Obesity is typically a consequence of overconsumption driven by an individual's natural sensitivity to food stimuli and the pleasure derived from eating. Intuitively, these processes should be effective targets for pharmacotherapy, and behavioral analysis can identify drugs that selectively affect desire to eat, enjoyment of eating, satiation or postmeal satiety. Rational interventions designed specifically to modulate these processes could limit the normally aversive consequences of caloric restriction and maximize an individual's capacity to successfully gain control over their appetite.

Key Points

  • Traditional antiobesity drug development focuses on weight and obesity-related disease end points, without adequate consideration of behavioral and psychological changes that initiate weight gain or that impede weight management

  • Classical energy homeostasis models emphasize energy regulation systems, but fail to acknowledge key motivational, emotional and behavioral factors that contribute to energy intake and the propensity to gain weight

  • Drug efficacy has been limited, as key behavioral features of appetite have been ignored—namely, hedonic aspects of consumption and the powerful influence of the environment in triggering overeating

  • Pharmaceutical companies are beginning to focus on treatments that combine existing compounds to exploit additive, or supra-additive, actions of separate agents

  • This approach could be advanced by exploiting the specific actions of drugs on distinct components of eating motivation rather than merely emphasizing simple effects on energy intake and body weight

  • Behavioral analysis can isolate drugs that reduce the desire to eat by acting on the processes that initiate, sustain and terminate meals or inhibit consumption

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References

  1. 1

    Brown, W. J., Williams, L., Ford, J. H., Ball, K. & Dobson, A. J. Identifying the energy gap: magnitude and determinants of 5-year weight gain in mid-age women. Obes. Res. 13, 1431–1441 (2005).

    PubMed  Article  Google Scholar 

  2. 2

    National Institute for Clinical Excellence. Obesity: the prevention, identification, assessment and management of overweight and obesity in adults and children [online], (2006).

  3. 3

    Pasman, W. J., Saris, W. H. & Westerterp-Plantenga, M. S. Predictors of weight maintenance. Obes. Res. 7, 43–50 (2006).

    Article  Google Scholar 

  4. 4

    Keys, A., Brozek, J., Henschel, A., Mickelsen, O. & Taylor, H. L. The Biology of Human Starvation (2 volumes) (University of Minnesota Press, Minneapolis, 1950).

    Google Scholar 

  5. 5

    Warren, C. & Cooper, P. J. Psychological effects of dieting. Br. J. Clin. Psychol. 27, 269–270 (1988).

    PubMed  Article  Google Scholar 

  6. 6

    Ogden, J. & Evans, C. The problem with weighing: Effects of mood, self-esteem and body image. Int. J. Obes. Relat. Metab. Disord. 20, 272–277 (1996).

    CAS  PubMed  Google Scholar 

  7. 7

    Laessle, R. G., Platte, P., Schweiger, U. & Pirke, K. M. Biological and psychological correlates of intermittent dieting behavior in young women. A model for bulimia nervosa. Physiol. Behav. 60, 1–5 (1996).

    CAS  PubMed  Article  Google Scholar 

  8. 8

    Halford, J. C. Clinical pharmacotherapy for obesity: current drugs and those in advanced development. Curr. Drug Targets 5, 637–646 (2004).

    CAS  PubMed  Article  Google Scholar 

  9. 9

    O'Donovan, D., Feinle-Bisset, C., Wishart, J. & Horowitz, M. Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects. Br. J. Nutr. 90, 849–852 (2003).

    CAS  PubMed  Article  Google Scholar 

  10. 10

    Swhwizer, A. et al. Role of lipase in the regulation of upper gastrointestinal function in humans. Am. J. Physiol. 273, G612–G620 (1997).

    Article  Google Scholar 

  11. 11

    Rosenbaum, M. et al. Low-dose leptin reverses sketetal muscle, autonomic, and neuroendocrine adaptation to maintenance of reduced body weight. J. Clin. Invest. 115, 3579–3586 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12

    Mars, M., de Graaf, C., de Groot, C. P., van Rossum, C. T. & Kok, F. J. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet. Int. J. Obes. 30, 122–128 (2006).

    CAS  Article  Google Scholar 

  13. 13

    Blundell, J. E. & Halford, J. C. Regulation of nutrient supply: the brain and appetite control. Proc. Nutr. Soc. 53, 407–418 (1994).

    CAS  PubMed  Article  Google Scholar 

  14. 14

    Halford, J. C. & Blundell, J. E. Separate systems for serotonin and leptin in appetite control. Ann. Med. 32, 222–232 (2000).

    CAS  PubMed  Article  Google Scholar 

  15. 15

    Mela, D. J. Eating for pleasure or just wanting to eat? Reconsidering sensory hedonic responses as a driver of obesity. Appetite 47, 10–17 (2006).

    PubMed  Article  Google Scholar 

  16. 16

    Finlayson, G., King, N. & Blundell, J. E. Liking vs wanting food: importance for human appetite control and weight regulation. Neurosci. Biobehav. Rev. 31, 987–1002 (2007).

    PubMed  Article  Google Scholar 

  17. 17

    Rankinen, T. et al. The human obesity gene map: The 2005 update. Obesity 14, 529–644 (2006).

    PubMed  Article  Google Scholar 

  18. 18

    O'Rahilly, S. & Farooqi, I. S. Genetics of obesity. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1095–1105 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19

    Blundell, J. E. et al. Resistance and susceptibility to weight gain: individual variability in response to a high fat diet. Physiol. Behav. 86, 614–622 (2005).

    CAS  PubMed  Article  Google Scholar 

  20. 20

    Wardle, J. et al. Obesity associated genetic variation in FTO is associated with diminished satiety. J. Clin. Endocrinol. Metab. 93, 3640–3643 (2008).

    CAS  PubMed  Article  Google Scholar 

  21. 21

    Cecil, J. E., Tavendale, R., Watt, P., Hetherington, M. M. & Palmer, C. N. An obesity-associated FTO gene variant and increased energy intake in children. N. Engl. J. Med. 359, 2558–2566 (2008).

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Wardle, J., Llewellyn, C., Sanderson, S. & Plomin, R. The FTO gene and measured food intake in children. Int. J. Obes. 33, 42–45 (2009).

    CAS  Article  Google Scholar 

  23. 23

    Haupt, A. et al. Variation in the FTO gene influences food intake but not energy expenditure. Exp. Clin. Endocrinol. Diabetes 117, 194–197 (2009).

    CAS  PubMed  Article  Google Scholar 

  24. 24

    Spiegel, T. A., Wadden, T. A. & Foster, G. D. Objective measurement of eating rate during behavioral treatment of obesity. Behav. Ther. 22, 61–67 (1991).

    Article  Google Scholar 

  25. 25

    Barkeling, B., Ekman, S. & Rössner, S. Eating behaviour in obese and normal weight 11-year-old children. Int. J. Obes. Relat. Metab. Disord. 16, 335–360 (1992).

    Google Scholar 

  26. 26

    Laessle, R. G., Lehrke, S. & Dückers, S. Laboratory eating behavior in obesity. Appetite 49, 399–404 (2007).

    PubMed  Article  Google Scholar 

  27. 27

    Meyer, J. E. & Pudel, V. Experimental studies on food-intake in obese and normal weight subjects. J. Psychosom. Res. 16, 305–308 (1972).

    CAS  PubMed  Article  Google Scholar 

  28. 28

    Stunkard, A. & Kaplan, D. Eating in public places: a review of reports of the direct observation of eating behavior. Int. J. Obes. 1, 89–101 (1977).

    CAS  PubMed  Google Scholar 

  29. 29

    Näslund, E., Gutniak, M., Skogar, S., Rössner, S. & Hellström, P. M. Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am. J. Clin. Nutr. 68, 525–530 (1998).

    PubMed  Article  Google Scholar 

  30. 30

    Lindgren, A. C. et al. Eating behaviour in Prader–Willi syndrome, normal weight and obese control groups. J. Pediatr. 137, 50–55 (2000).

    CAS  PubMed  Article  Google Scholar 

  31. 31

    Williamson, D. A. et al. Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite 45, 75–80 (2005).

    CAS  PubMed  Article  Google Scholar 

  32. 32

    Otsuka, R. et al. Eating fast leads to obesity: Findings based on self-administered questionnaires among middle-aged Japanese men and women. J. Epidemiol. 16, 117–124 (2006).

    PubMed  Article  Google Scholar 

  33. 33

    Maruyama, K. et al. The joint impact on being overweight of self reported behaviours of eating quickly and eating until full: cross sectional survey. BMJ 337, a2002 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34

    Llewellyn, C. H., van Jaarsveld, C. H., Boniface, D., Carnell, S. & Wardle, J. Eating rate is a heritable phenotype related to weight in children. Am. J. Clin. Nutr. 88, 1560–1566 (2008).

    CAS  PubMed  Article  Google Scholar 

  35. 35

    Pearcey, S. M. & de Castro, J. M. Food intake and meal patterns of weight-stable and weight-gaining persons. Am. J. Clin. Nutr. 76, 107–112 (2002).

    CAS  PubMed  Article  Google Scholar 

  36. 36

    Rissanen, A. et al. Acquired preference especially for dietary fat and obesity: a study of weight-discordant monozygotic twin pairs. Int. J. Obes. Relat. Metab. Disord. 26, 973–977 (2002).

    CAS  PubMed  Article  Google Scholar 

  37. 37

    Bray, G. A., Paeratakul, S. & Popkin, B. M. Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol. Behav. 83, 549–555 (2004).

    CAS  PubMed  Article  Google Scholar 

  38. 38

    Kral, T. V., Roe, L. S. & Rolls, B. J. Combined effects of energy density and portion size on energy intake in women. Am. J. Clin. Nutr. 79, 962–968 (2004).

    CAS  PubMed  Article  Google Scholar 

  39. 39

    Geliebter, A. & Hashim, S. A. Gastric capacity in normal obese, and bulimic women. Physiol. Behav. 74, 743–746 (2001).

    CAS  PubMed  Article  Google Scholar 

  40. 40

    Geliebter, A., Yahav, E. K., Gluck, M. E. & Hashim, S. A. Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder. Physiol. Behav. 81, 735–740 (2004).

    CAS  PubMed  Article  Google Scholar 

  41. 41

    Ranganath, L. R. et al. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut 38, 916–919 (1996).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42

    De Graaf, C., Blom, W. A., Smeets, P. A., Staflue, A. & Hendricks, H. F. Biomarkers of satiation and satiety. Am. J. Clin. Nutr. 17, 949–961 (2004).

    Google Scholar 

  43. 43

    Adam, T. C. & Westerterp-Plantenga, M. S. Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese. Br. J. Nutr. 93, 845–851 (2005).

    CAS  PubMed  Article  Google Scholar 

  44. 44

    le Roux, C. W. et al. Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 147, 3–8 (2006).

    CAS  PubMed  Article  Google Scholar 

  45. 45

    Blundell, J. E. et al. Over-consumption and obesity: peptides and susceptibility to weight gain. Regul. Pept. 149, 32–38 (2008).

    CAS  PubMed  Article  Google Scholar 

  46. 46

    Matsuda, M. et al. Altered hypothalamic function in response to glucose ingestion in obese humans. Diabetes 48, 1801–1806 (1999).

    CAS  PubMed  Article  Google Scholar 

  47. 47

    Gautier, J. F. et al. Differential brain responses to satiation in obese and lean men. Diabetes 49, 838–846 (2000).

    CAS  PubMed  Article  Google Scholar 

  48. 48

    Carnell, S. & Wardle, J. Appetite and adiposity in children: evidence for a behavioral susceptibility theory of obesity. Am. J. Clin. Nutr. 88, 22–29 (2008).

    CAS  PubMed  Article  Google Scholar 

  49. 49

    Halford, J. C. et al. Beyond-brand effect of television food advertisements on food choice in children: the effects of weight status. Public Health Nutr. 11, 897–904 (2008).

    PubMed  Article  Google Scholar 

  50. 50

    Rothemund, Y. et al. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. Neuroimage 37, 410–421 (2007).

    Article  PubMed  Google Scholar 

  51. 51

    Stoeckel, L. E. et al. Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage 41, 636–647 (2008).

    PubMed  Article  Google Scholar 

  52. 52

    Drewnowski, A., Brunzell, J. D., Sande, K., Iverise, K. & Greenwood, M. R. Sweet tooth reconsidered: taste responsiveness in human obesity. Physiol. Behav. 35, 617–622 (1985).

    CAS  PubMed  Article  Google Scholar 

  53. 53

    Mela, D. J. & Sacchetti, D. A. Sensory preference for fats: relationships with diet and body composition. Am. J. Clin. Nutr. 53, 908–915 (1991).

    CAS  PubMed  Article  Google Scholar 

  54. 54

    Blundell, J. E. & Finlayson, G. Is susceptibility to weight gain characterized by homeostatic or hedonic risk factors for over-consumption? Physiol. Behav. 82, 21–25 (2004).

    CAS  PubMed  Article  Google Scholar 

  55. 55

    Hill, A. J., Rogers, P. J. & Blundell, J. E. Techniques for the experimental measurement of human eating behaviour and food intake: a practical guide. Int. J. Obes. Relat. Metab. Disord. 19, 361–375 (1995).

    CAS  PubMed  Google Scholar 

  56. 56

    Blundell, J. E. et al. in Handbook of Assessment Methods for Eating Behaviors and Weight-Related Problems: Measures, Theory, and Research (eds Allison, D. B. & Baskin, M. L.) 283–326 (Sage Publications Inc., Thousand Oaks, 2009).

    Google Scholar 

  57. 57

    Halford, J. C., Harrold, J. A., Boyland, E. J., Lawton, C. L. & Blundell, J. E. Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 67, 27–55 (2007).

    CAS  PubMed  Article  Google Scholar 

  58. 58

    Flint, A., Raben, A., Blundell, J. E. & Astrup, A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in a single test meal studies. Int. J. Obes. Relat. Metab. Disord. 24, 38–48 (2000).

    CAS  PubMed  Article  Google Scholar 

  59. 59

    Stubbs, R. J. et al. The use of visual analogue scales to assess motivation to eat in human subjects: A review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br. J. Nutr. 84, 405–415 (2000).

    CAS  PubMed  Article  Google Scholar 

  60. 60

    Drapeau, V. et al. Appetite sensations as a marker of overall intake. Br. J. Nutr. 93, 273–280 (2005).

    CAS  PubMed  Article  Google Scholar 

  61. 61

    Drapeau, V. et al. Appetite sensations and satiety quotient: predictors of energy intake and weight loss. Appetite 48, 159–166 (2007).

    PubMed  Article  Google Scholar 

  62. 62

    Rogers, P. J. & Blundell, J. E. Effect of anorexic drugs on food intake and the micro-structure of eating in human subjects. Psychopharmacology 66, 159–165 (1979).

    CAS  PubMed  Article  Google Scholar 

  63. 63

    Yeomans, M. R. & Gray, R. W. Effects of naltrexone on food intake and changes in subjective appetite during eating: Evidence for opioid involvement in the appetizer effect. Physiol. Behav. 62, 15–21 (1997).

    CAS  PubMed  Article  Google Scholar 

  64. 64

    Halford, J. C. et al. The effects of sibutramine on the microstructure of feeding behaviour as measured by the Universal Eating Monitor (UEM). J. Psychopharmacol. 24, 99–109 (2010).

    CAS  PubMed  Article  Google Scholar 

  65. 65

    Erondu, N. et al. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab. 4, 275–282 (2006).

    CAS  PubMed  Article  Google Scholar 

  66. 66

    King, N. A., Lawton, C. L., Delargy, H. J., Smith, F. C. & Blundell, J. E. in Ingestive Behavior Protocols (eds Wellmann, P. J. & Hoebel, B. G.) 71–76 (Society for the Study of Ingestive Behavior, New York, 1997).

    Google Scholar 

  67. 67

    Stubbs, R. J. et al. Description and evaluation of a Newton-based electronic appetite rating system for temporal tracking of appetite in human subjects. Physiol. Behav. 72, 615–619 (2001).

    CAS  PubMed  Article  Google Scholar 

  68. 68

    Bolger, N., Davis, A. & Rafaeli, E. Diary methods: capturing life as it is lived. Annu. Rev. Psychol. 54, 579–616 (2003).

    PubMed  Article  Google Scholar 

  69. 69

    Burton, C., Weller, D. & Sharpe, M. Are electronic diaries useful for symptoms research? A systematic review. J. Psychosom. Res. 62, 553–561 (2007).

    PubMed  Article  Google Scholar 

  70. 70

    Shiffman, S., Stone, A. A. & Hufford, M. R. Ecological momentary assessment. Annu. Rev. Clin. Psychol. 4, 1–32 (2008).

    PubMed  Article  Google Scholar 

  71. 71

    Ebner-Priemer, U. W. & Trull, T. J. Ambulatory assessment: An innovative and promising approach for clinical psychology. European Psychol. 14, 109–119 (2009).

    Article  Google Scholar 

  72. 72

    Cappelleri, J. C. et al. Evaluating the Power of Food Scale in obese subjects and a general sample of individuals: development and measurement properties. Int. J. Obes. 33, 913–922 (2009).

    CAS  Article  Google Scholar 

  73. 73

    Cappelleri, J. C. et al. Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants. Int. J. Obes. 33, 611–620 (2009).

    CAS  Article  Google Scholar 

  74. 74

    Karlsson, J., Persson, L. O., Sjöström, L. & Sullivan, M. Psychometric properties and factor structure of the three-factor eating questionnaire (TFEQ) in obese men and women, results from the Swedish obese subjects (SOS) study. Int. J. Obes. 24, 1715–1725 (2000).

    CAS  Article  Google Scholar 

  75. 75

    Barkeling, B., King, N. A., Näslund, E. & Blundell, J. E. Characterization of obese individuals who claim to detect no relationship between their eating pattern and sensations of hunger or fullness. Int. J. Obes. 31, 435–439 (2007).

    CAS  Article  Google Scholar 

  76. 76

    Provencher, V., Drapeau, V., Tremblay, A., Després, J. P. & Lemieux, S. Eating behaviors and indexes of body composition in men and women from the Quebéc family study. Obes. Res. 11, 783–792 (2003).

    PubMed  Article  Google Scholar 

  77. 77

    Dykes, J., Brunner, E. J., Martikeainene, P. T. & Wardle, J. Socioeconomic gradient in body size and oboist among women: The role of dietary restraint, disinhibition and hunger in the Whitehall II study. Int. J. Obes. Relat. Metab. Disord. 28, 262–268 (2004).

    CAS  PubMed  Article  Google Scholar 

  78. 78

    Lawson, O. J. et al. The association of body weight, dietary intake, and energy expenditure with dietary restraint and disinhibition. Obes. Res. 3, 153–161 (1995).

    CAS  PubMed  Article  Google Scholar 

  79. 79

    Williamson, D. A. et al. Association of body mass with dietary restraint and disinhibition. Appetite 25, 31–41 (1995).

    CAS  PubMed  Article  Google Scholar 

  80. 80

    Hays, N. P. et al. Eating behaviour correlates of adult weight gain and obesity in healthy women aged 55–65 y. Am. J. Clin. Nutr. 75, 476–483 (2002).

    CAS  PubMed  Article  Google Scholar 

  81. 81

    Bellisle, F. et al. The eating inventory and body adiposity from leanness to massive obesity: A study of 2509 adults. Obes. Res. 12, 2023–2030 (2004).

    PubMed  Article  Google Scholar 

  82. 82

    Borg, P., Fogelholm, M. & Kukkonen-Harjula, K. Food selection and eating behaviour during weight maintenance intervention and 2-y follow-up in obese men. Int. J. Obes. Relat. Metab. Disord. 28, 1548–1554 (2004).

    CAS  PubMed  Article  Google Scholar 

  83. 83

    Provencher, V. et al. Familial resemblance in eating behaviors in men and women from the Quebéc family study. Obes. Res. 13, 1624–1629 (2005).

    PubMed  Article  Google Scholar 

  84. 84

    Bouchard, L. et al. Neuromedin β: a strong candidate gene linking eating behaviors and susceptibility to obesity. Am. J. Clin. Nutr. 80, 1478–1486 (2004).

    CAS  PubMed  Article  Google Scholar 

  85. 85

    Stunkard, A. J. Eating patterns in obesity. Psychiatr. Q. 33, 284–292 (1959).

    CAS  PubMed  Article  Google Scholar 

  86. 86

    Hsu, L. K. et al. Binge eating disorder in extreme obesity. Int. J. Obes. Relat. Metab. Disord. 26, 1398–1403 (2002).

    CAS  PubMed  Article  Google Scholar 

  87. 87

    Grucza, R. A., Przybeck, T. R. & Cloninger, C. R. Prevalence and correlates of binge eating disorder in a community sample. Compr. Psychiatr. 48, 124–131 (2007).

    Article  Google Scholar 

  88. 88

    Elfhag, K. & Rössner, S. Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain. Obes. Rev. 6, 67–85 (2005).

    CAS  PubMed  Article  Google Scholar 

  89. 89

    Bryant, E. J., King, N. A. & Blundell, J. E. Disinhibition: its effects on appetite and weight regulation. Obes. Rev. 9, 409–419 (2008).

    CAS  PubMed  Article  Google Scholar 

  90. 90

    Elfhag, K., Rössner, S., Barkeling, B. & Rooth, P. Sibutramine treatment in obesity: initial eating behaviour in relation to weight loss results and changes in mood. Pharmacol. Res. 51, 159–163 (2005).

    CAS  PubMed  Article  Google Scholar 

  91. 91

    Elfhag, K., Finer, N. & Rössner, S. Who will lose weight on sibutramine and orlistat? Psychological correlates for treatment success. Diabetes Obes. Metab. 10, 498–505 (2008).

    CAS  PubMed  Article  Google Scholar 

  92. 92

    Wren, A. M. et al. Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 86, 5992–5995 (2001).

    CAS  PubMed  Article  Google Scholar 

  93. 93

    Ballinger, A., McLoughlin, L., Medbak, S. & Clark, M. Cholecystokinin is a satiety hormone in humans at physiological postprandial plasma concentrations. Clin. Sci. 89, 375–381 (1995).

    CAS  PubMed  Article  Google Scholar 

  94. 94

    Batterham, R. L. et al. Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418, 650–654 (2002).

    CAS  Article  Google Scholar 

  95. 95

    English, P. J., Ghatei, M. A., Malik, I. A., Bloom, S. R. & Wilding, J. P. Food fails to suppress ghrelin levels in obese humans. J. Clin. Endocrinol. Metab. 87, 2984–2987 (2002).

    CAS  PubMed  Article  Google Scholar 

  96. 96

    Jordan, J. et al. Stimulation of cholecystokinin-A receptors with GI181771X does not cause weight loss in overweight or obese patients. Clin. Pharmacol. Ther. 83, 281–287 (2008).

    CAS  PubMed  Article  Google Scholar 

  97. 97

    Bojanowska, E. Physiology and pathophysiology of glucagon-like peptide 1 (GLP-1): the role of GLP-1 in the pathogenesis of diabetes mellitus, obesity, and stress. Med. Sci. Monit. 11, RA271–RA278 (2005).

    CAS  PubMed  Google Scholar 

  98. 98

    Nauck, M. A. et al. Glucagon-like peptide-1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am. J. Physiol. Endocrinol. Metab. 273, E981–E988 (1997).

    CAS  Article  Google Scholar 

  99. 99

    Little, T. J. et al. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. J. Clin. Endocrinol. Metab. 91, 1916–1923 (2006).

    CAS  PubMed  Article  Google Scholar 

  100. 100

    Flint, A., Raben, A., Astrup, A. & Holst, J. J. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest. 101, 515–520 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. 101

    Gutzwiller, J. P. et al. Glucagon-like peptide-1: a potent regulator of food intake in humans. Gut 44, 81–86 (1999).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. 102

    Degen, L. et al. Effects of a preload on reduction of food intake by GLP-1 in healthy subjects. Digestion 74, 78–84 (2006).

    CAS  PubMed  Article  Google Scholar 

  103. 103

    Gutzwiller, J. P., Degen, L., Matzinger, D., Prestin, S. & Beglinger, C. Interaction between GLP-1 and CCK-33 in inhibiting food intake and appetite in men. Am. J. Physiol. Regul. Comp. Physiol. 287, R562–R567 (2004).

    CAS  Article  Google Scholar 

  104. 104

    Näslund, E., Gutniak, M., Skogar, S., Rössner, S. & Hellström, P. M. Glucagon-like peptide 1 increase the period of postprandial satiety and slows gastric emptying in obese men. Am. J. Clin. Nutr. 68, 525–530 (1998).

    PubMed  Article  Google Scholar 

  105. 105

    Näslund, E. et al. Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int. J. Obes. Relat. Metab. Disord. 23, 304–311 (1999).

    PubMed  Article  Google Scholar 

  106. 106

    Näslund, E. et al. Prandial subcutaneous injections of glucagon like peptide 1 cause weight loss in obese human subjects. Br. J. Nutr. 91, 439–446 (2004).

    PubMed  Article  CAS  Google Scholar 

  107. 107

    Gutzwiller, J. P. et al. Glucagon-like peptide-1 promotes satiety and reduced food intake in patients with diabetes mellitus. Am. J. Physiol. 276, R1541–R1545 (1999).

    CAS  PubMed  Google Scholar 

  108. 108

    Flint, A., Raben, A., Ersbøll, A. K., Holst, J. J. & Astrup, A. The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int. J. Obes. Relat. Metab. Disord. 25, 781–792 (2001).

    CAS  PubMed  Article  Google Scholar 

  109. 109

    Edwards, C. M. et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am. J. Physiol. Endocrinol. Metab. 291, E155–E161 (2001).

    Article  Google Scholar 

  110. 110

    Madsbad, S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)—preclinical and clinical results. Best Pract. Res. Clin. Endocrinol. Metab. 23, 463–477 (2009).

    CAS  PubMed  Article  Google Scholar 

  111. 111

    Hanssen, K. B., Knop, F. K., Holst, J. J. & Vilsbøll, T. Treatment of type 2 diabetes with glucagon-like peptide-1 receptor agonists. Int. J. Clin. Pract. 63, 1154–1160 (2009).

    Article  CAS  Google Scholar 

  112. 112

    Cohen, M. A. et al. Oxyntomodulin suppresses appetite and reduced food intake in humans. J. Clin. Endocrinol. Metab. 88, 4696–4701 (2003).

    CAS  PubMed  Article  Google Scholar 

  113. 113

    Wynne, K. et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int. J. Obes. 30, 1729–1736 (2006).

    CAS  Article  Google Scholar 

  114. 114

    Wynne, K. et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes 54, 2390–2395 (2005).

    CAS  PubMed  Article  Google Scholar 

  115. 115

    Onga, T., Zabielski, R. & Kato, S. Multiple regulation of peptide YY secretion in the digestive tract. Peptides 23, 279–290 (2002).

    Article  Google Scholar 

  116. 116

    Renshaw, D. & Batterham, R. L. Peptide YY: a potential therapy for obesity. Curr. Drug Targets 6, 171–179 (2005).

    CAS  PubMed  Article  Google Scholar 

  117. 117

    Baggiano, M. M. et al. PYY3–36 as an anti-obesity drug target. Obes. Rev. 6, 307–322 (2005).

    Article  Google Scholar 

  118. 118

    Batterham, R. L. et al. Inhibition of food intake in obese subjects by peptide YY3–36 . N. Engl. J. Med. 349, 914–918 (2003).

    Article  Google Scholar 

  119. 119

    Batterham, R. L. et al. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature 450, 106–109 (2007).

    CAS  Article  PubMed  Google Scholar 

  120. 120

    le Roux, C. W. et al. Supraphysiological doses of intravenous PYY3–36 cause nausea, but no additional reduction in food intake. Ann. Clin. Biochem. 45, 93–95 (2008).

    CAS  PubMed  Article  Google Scholar 

  121. 121

    Degen, L. et al. Effect of peptide PYY3–36 on food intake in humans. Gastroenterology 129, 1430–1436 (2005).

    CAS  PubMed  Article  Google Scholar 

  122. 122

    Sloth, B., Davidson, L., Holst, J. J., Flint, A. & Astrup, A. Effect of subcutaneous injections of PYY1–36 and PYY3–36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males. Am. J. Physiol. Endocrinol. Metab. 293, E604–E609 (2007).

    CAS  PubMed  Article  Google Scholar 

  123. 123

    Sloth, B., Holst, J. J., Flint, A., Gregersen, N. T. & Astrup, A. Effects of PYY1–36 and PYY3–36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects. Am. J. Physiol. Endocrinol. Metab. 292, E1062–E1068 (2007).

    CAS  PubMed  Article  Google Scholar 

  124. 124

    Chapman, I. et al. Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects. Obesity 15, 1179–1186 (2007).

    CAS  PubMed  Article  Google Scholar 

  125. 125

    Reda, T. K., Geliebter, A. & Pi-Sunyer, F. X. Amylin, food intake and obesity. Obes. Res. 10, 1087–1091 (2002).

    CAS  PubMed  Article  Google Scholar 

  126. 126

    Lutz, T. A. Pancreatic amylin as a centrally acting satiating hormone. Curr. Drug Targets 6, 181–189 (2005).

    CAS  PubMed  Article  Google Scholar 

  127. 127

    Chapman, I. et al. Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia 48, 838–848 (2005).

    CAS  PubMed  Article  Google Scholar 

  128. 128

    Smith, S. R. et al. Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study. Am. J. Physiol. Endocrinol. Metab. 293, E620–E627 (2007).

    CAS  PubMed  Article  Google Scholar 

  129. 129

    Hollander, P. et al. Addition of pramlintide to insulin therapy lowers HbA1c in conjunction with weight loss in patients with type 2 diabetes approaching glycaemic targets. Diabetes Obes. Metab. 5, 408–414 (2003).

    CAS  PubMed  Article  Google Scholar 

  130. 130

    Hollander P. et al. Effect of pramlintide on weight in overweight and obese insulin treated type 2 diabetes patients. Obes. Res. 12, 661–668 (2004).

    CAS  PubMed  Article  Google Scholar 

  131. 131

    Farooqi, I. S. et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med. 341, 879–884 (1999).

    CAS  Article  Google Scholar 

  132. 132

    Williamson, D. A. et al. Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite 45, 75–80 (2005).

    CAS  PubMed  Article  Google Scholar 

  133. 133

    Ravussin, E. et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity 17, 1736–1743 (2009).

    CAS  PubMed  Article  Google Scholar 

  134. 134

    Abenhaim, L. et al. Appetite suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N. Engl. J. Med. 335, 609–616 (1996).

    CAS  PubMed  Article  Google Scholar 

  135. 135

    Rothman, R. B. & Baumann, M. H. Serotonergic drugs and valvular heart disease. Expert Opin. Drug Saf. 8, 317–329 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  136. 136

    Rolls, B. J., Shide, D. J., Thorwart, M. L. & Ulbrecht, J. S. Sibutramine reduces food intake in non-dieting women with obesity. Obes. Res. 6, 1–11 (1998).

    CAS  PubMed  Article  Google Scholar 

  137. 137

    Barkeling, B., Elfhag, K., Rooth, P. & Rössner, S. Short-term effects of sibutramine (Reductil™) on appetite and eating behaviour and the long-term therapeutic outcomes. Int. J. Obes. Relat. Metab. Disord. 27, 693–700 (2003).

    CAS  PubMed  Article  Google Scholar 

  138. 138

    Appolinario, J. C. et al. A randomized, double-blind, placebo-controlled study of sibutramine in the treatment of binge-eating disorder. Arch. Gen. Psychiatry 60, 1109–1116 (2003).

    CAS  PubMed  Article  Google Scholar 

  139. 139

    Appolinario, J. C. et al. An open-label trial of sibutramine in obese patients with binge-eating disorder. J. Clin. Psychiatry 63, 28–30 (2002).

    CAS  PubMed  Article  Google Scholar 

  140. 140

    Milano, W. et al. Use of sibutramine, an inhibitor of the reuptake of serotonin and noradrenaline, in the treatment of binge eating disorder: A placebo-controlled study. Adv. Ther. 22, 25–31 (2005).

    CAS  PubMed  Article  Google Scholar 

  141. 141

    Taflinski, T. & Chojnacka, J. Sibutramine-associated psychotic episode. Am. J. Psychiatry 157, 2057–2058 (2000).

    CAS  PubMed  Article  Google Scholar 

  142. 142

    Binkley, K. & Knowles, S. R. Sibutramine and panic attacks. Am. J. Psychiatry 159, 1793–1794 (2002).

    PubMed  Article  Google Scholar 

  143. 143

    Sharma, S. M. et al. Blood pressure changes associated with sibutramine and weight management – an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes trial (SCOUT). Diabetes Obes. Metab. 11, 239–250 (2009).

    CAS  PubMed  Article  Google Scholar 

  144. 144

    Heisler, L. K. et al. Activation of central melanocortin pathways by fenfluramine. Science 297, 609–611 (2002).

    CAS  Article  Google Scholar 

  145. 145

    Heisler, L. K. et al. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51, 239–249 (2006).

    CAS  PubMed  Article  Google Scholar 

  146. 146

    Walsh, A. E. et al. m-Chlorophenylpiperazine decreases food intake in a test meal. Psychopharmacology 116, 120–122 (1994).

    CAS  PubMed  Article  Google Scholar 

  147. 147

    Cowen, P. J., Sargent, P. A., Williams, C., Goodall, E. M. & Orlikov, A. B. Hypophagic, endocrine and subjective responses to m-chlorophenylpiperazine in healthy-men and women. Hum. Psychopharmacol. 10, 385–391 (1995).

    CAS  Article  Google Scholar 

  148. 148

    Sargent, P. A., Sharpley, A. L., Williams, C., Goodall, E. M. & Cowen, P. J. 5-HT2C activation decreases appetite and body weight in obese subjects. Psychopharmacology 133, 309–312 (1997).

    CAS  PubMed  Article  Google Scholar 

  149. 149

    Ghaziuddin, N., Welch, K. & Greden, J. Central serotonergic effects of m-chlorophenylpiperazine (mCPP) among normal control adolescents. Neuropsychopharmacology 28, 133–139 (2003).

    CAS  PubMed  Article  Google Scholar 

  150. 150

    Smith, B. M. et al. Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity. Bioorg. Med. Chem. Lett. 15, 1467–1470 (2005).

    CAS  PubMed  Article  Google Scholar 

  151. 151

    Smith, S. R. et al. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity 17, 494–503 (2009).

    CAS  PubMed  Article  Google Scholar 

  152. 152

    Doggrell, S. A. Tesofensine—a novel potent weight loss medication. Expert Opinion Invest. Drugs 18, 1043–1046 (2009).

    CAS  Article  Google Scholar 

  153. 153

    Bello, N. T. & Zahner, M. R. Tesofensine, a monoanime reuptake inhibitor for the treatment of obesity. Curr. Opinion Investig. Drugs 10, 1105–1116 (2009).

    CAS  Google Scholar 

  154. 154

    Hauser, R. A., Saline, L., Judel, N., Konyago, V. L. & The NS 2330 Monotherepy PC Study Group. Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease. Mov. Disord. 22, 359–365 (2007).

    PubMed  Article  Google Scholar 

  155. 155

    Astrup, A. et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 372, 1906–1913 (2008).

    CAS  PubMed  Article  Google Scholar 

  156. 156

    Gasteyger, C., Sjödin, A., Meier, D. H. & Astrup, A. Effects of tesofensine on appetite in obese subjects. Obesity 16 (Suppl. 1), S138–S139 (2008).

    Google Scholar 

  157. 157

    Sommet, A., Pathak, A. & Montastruc, J. L. Tesofensine and weight loss. Lancet 373, 719 (2009).

    PubMed  Article  Google Scholar 

  158. 158

    Astrup, A., Madsbad, S. & Larsen, T. M. Tesofensine and weight loss—Authors' reply. Lancet 373, 720 (2009).

    Article  Google Scholar 

  159. 159

    Kalra, S. P. et al. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr. Rev. 20, 68–100 (1999).

    CAS  PubMed  Google Scholar 

  160. 160

    Berthoud, H. R. & Morrison, C. The brain, appetite and obesity. Annu. Rev. Psychol. 59, 55–92 (2008).

    PubMed  Article  Google Scholar 

  161. 161

    Kamiji, M. M. & Inui, A. Neuropeptide Y receptor selective ligands in the treatment of obesity. Endocr. Rev. 28, 664–684 (2007).

    CAS  PubMed  Article  Google Scholar 

  162. 162

    Jeon, M. K. & Cheon, H. G. Promising strategies for obesity pharmacotherapy: melanocortin-4 (MC-4) receptor agonists and melanin concentrating hormone (MCH) receptor-1 antagonists. Curr. Top. Med. Chem. 9, 504–538 (2009).

    CAS  PubMed  Article  Google Scholar 

  163. 163

    ClinicalTrials.gov. Phase IIb one year efficacy and safety study of S-2367 (Velneperit) in obese subjects with initial 6-week low calorie diet (LDC) [online], (2009).

  164. 164

    Shionogi & Co., Ltd. Shionogi announces positive top-line efficacy results from year-long studies of velneperit, a novel NPY Y5 receptor antagonist being investigated for the treatment of obesity [online], (2009).

  165. 165

    Drewnowski, A., Krahn, D. D., Demitrack, M. A., Nairn, K. & Gosnell, B. A. Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters. Am. J. Clin. Nutr. 61, 1206–1212 (1995).

    CAS  PubMed  Article  Google Scholar 

  166. 166

    Yeomans, M. R. & Gray, R. W. Selective effects of naltrexone on food pleasantness and intake. Physiol. Behav. 60, 439–446 (1996).

    CAS  PubMed  Article  Google Scholar 

  167. 167

    Yeomans, M. R. & Gray, R. W. Effects of naltrexone on food intake and changes in subjective appetite during eating: Evidence for opioid involvement in the appetizer effect. Physiol. Behav. 62, 15–21 (1997).

    CAS  PubMed  Article  Google Scholar 

  168. 168

    Yeomans, M. R., Wright, P., Macleod, H. A. & Critchley, J. A. Effects of nalmefene on feeding in humans—dissociation of hunger and palatability. Psychopharmacology 100, 426–432 (1990).

    CAS  PubMed  Article  Google Scholar 

  169. 169

    Yeomans, M. R. & Wright, P. Lower pleasantness of palatable foods in nalmefene-treated human volunteers. Appetite 16, 249–259 (1991).

    CAS  PubMed  Article  Google Scholar 

  170. 170

    Speigal, T. A. et al. Effect of naltrexone on food intake, hunger, and satiety in obese men. Physiol. Behav. 40, 135–141 (1987).

    Article  Google Scholar 

  171. 171

    Alger, S. A., Schwalberg, M. D., Bigaouette, J. M., Michalek, A. V. & Howard, L. J. Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects. Am. J. Clin. Nutr. 53, 865–871 (1991).

    CAS  PubMed  Article  Google Scholar 

  172. 172

    Lee, M. W. & Fujioka, K. Naltrexone for the treatment of obesity: review and update. Expert Opin. Pharmacother. 10, 1841–1845 (2009).

    CAS  PubMed  Article  Google Scholar 

  173. 173

    Kirkham, T. C. Endocannabinoids in the regulation of appetite and body weight. Behav. Pharmacol. 16, 297–313 (2005).

    CAS  PubMed  Article  Google Scholar 

  174. 174

    Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W. & Fischman, M. W. Abstinence symptoms following oral THC administration to humans. Psychopharmacol. 141, 385–394 (1999).

    CAS  Article  Google Scholar 

  175. 175

    Kirkham, T. C., Townson, A. L. & Halford, J. C. Oromucosal application of a cannabis extract accentuates pre-prandial hunger and increases caloric intake in healthy volunteers. Int. J. Obes. 31 (Suppl. 1), T2:PO.86, S99 (2007).

    Google Scholar 

  176. 176

    Van Gaal, L. F., Rissanen, A. M., Scheen, A. J., Ziegler, O. & Rossner, S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365, 1389–1397 (2005).

    CAS  PubMed  Article  Google Scholar 

  177. 177

    Pi-Sunyer, X., Despres, J. P., Scheen, A. & Van Gaal, L. Improvement of metabolic parameters with rimonabant beyond the effect attributable to weight loss alone: Pooled 1-year data from the RIO (rimonabant in obesity and related metabolic disorders) program. J. Am. Coll. Cardiol. 47 (Suppl. A), 362A (2006).

    Google Scholar 

  178. 178

    Pi-Sunyer, F. X. et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: A randomized controlled trial. JAMA. 295, 761–775 (2006).

    CAS  PubMed  Article  Google Scholar 

  179. 179

    Scheen, A. J., Finer, N., Hollander, P., Jensen, M. D. & Van Gaal, L. F. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 368, 1660–1672 (2006).

    CAS  PubMed  Article  Google Scholar 

  180. 180

    Blundell, J. E. et al. Effect of rimonabant on energy intake, motivation to eat and body weight with or without hypocaloric diet: the REBA study. Obes. Rev. 7 (Suppl. 2), PP0021, 104 (2006).

    Google Scholar 

  181. 181

    Addy, C. et al. Multiple-dose pharmacokinetics, pharmacodynamics, and safety of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, in healthy male volunteers. J. Clin. Pharmacol. 48, 734–744 (2008).

    CAS  PubMed  Article  Google Scholar 

  182. 182

    Plodowski, R. A. et al. Bupropion and naltrexone: a review of their use individually and in combination for the treatment of obesity. Expert Opin. Pharmacother. 10, 1069–1081 (2009).

    Article  Google Scholar 

  183. 183

    Hausenloy, D. J. Contrave™: a novel treatment for obesity. Clin. Lipidol. 4, 279–285 (2009).

    CAS  Article  Google Scholar 

  184. 184

    Jain, A. K. et al. Buproprion SR vs placebo for weight loss in obese patients with depressive symptoms. Obes. Res. 10, 1049–1056 (2002).

    CAS  PubMed  Article  Google Scholar 

  185. 185

    Anderson, J. W. et al. Buproprion SR enhances weight loss: A 48-week double blind, placebo-controlled trial. Obes. Res. 10, 633–641 (2002).

    CAS  PubMed  Article  Google Scholar 

  186. 186

    Li, Z. et al. Meta-analysis: pharmacologic treatments of obesity. Ann. Intern. Med. 142, 532–546 (2005).

    CAS  PubMed  Article  Google Scholar 

  187. 187

    Silverstone, T. Anorectic effect of a long-acting preparation of phentermine (duromine). Psychopharmacologica 25, 315–320 (1972).

    CAS  Article  Google Scholar 

  188. 188

    Van Ameringen, M., Mancini, C., Pipe, B., Campbell, M. & Oakman, J. Topiramate treatment for SSRI-incuded weight gain in anxiety disorders. J. Clin. Psychiatry 63, 981–984 (2002).

    CAS  PubMed  Article  Google Scholar 

  189. 189

    Ben-Menachem, A., Axelsen, M., Johanson, E. H., Stagge, A. & Smith, U. Predictors of weight loss in adults with topiramate-treated epilepsy. Obes. Res. 11, 556–562 (2003).

    CAS  PubMed  Article  Google Scholar 

  190. 190

    Gadde, K. M., Francisey, D. M., Wagner, H. R. & Krishnan, K. R. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA 289, 1820–1825 (2003).

    CAS  PubMed  Article  Google Scholar 

  191. 191

    Appolinario, J. C. & McElroy, S. L. Pharmacological approaches in the treatment of binge eating disorder. Curr. Drug Targets 5, 301–307 (2004).

    CAS  PubMed  Article  Google Scholar 

  192. 192

    Bray, G. A. et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes. Res. 11, 722–733 (2003).

    CAS  PubMed  Article  Google Scholar 

  193. 193

    Wilding, J. et al. A randomised 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 (2004).

    CAS  PubMed  Article  Google Scholar 

  194. 194

    McElroy, S. L. et al. Role of antiepileptic drugs in the management of eating disorders. CNS Drugs 23, 139–156 (2009).

    CAS  PubMed  Article  Google Scholar 

  195. 195

    Neary, N. M. et al. Peptide YY3–36 and glucagon-like peptide-1(7–36) inhibit food intake additively. Endocrinology 146, 5120–5127 (2005).

    CAS  PubMed  Article  Google Scholar 

  196. 196

    Rosenbaum, M., Sy, M., Pavlovich, K., Leibel, R. L. & Hirsch, J. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J. Clin. Invest. 118, 2583–2591 (2008).Ut nos adiatinit,

    CAS  PubMed  PubMed Central  Google Scholar 

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  1. School of Psychology, University of Liverpool, Eleanor Rathbone Building, Bedford Street South, Liverpool, L69 7ZA, UK

    Jason C. G. Halford, Emma J. Boyland, Tim C. Kirkham & Joanne A. Harrold

  2. Institute of Psychological Sciences, Faculty of Medicine and Health, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK

    John E. Blundell

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Competing interests

J. C. G. Halford declares associations with the following companies/organizations: GlaxoSmithKline (Speakers Bureau), Novo Nordisk (Speakers Bureau), Prosidion OSI Pharmaceuticals (Consultant). J. E. Blundell is an expert consultant to the NDA Panel of the European Food Safety Authority (EFSA), a Scientific Governor of the British Nutrition Foundation, and Treasurer and Trustee of the European Association for the Study of Obesity. He is also an advisor/consultant to industrial companies in the food and pharmaceutical sectors (Consultant: Merck, Amylin, Covance, Barilla, Danone; Speakers bureau: Kellogg's, Fonterra; Grant/research support: National Starch, Coca-Cola, Sanofi-aventis, Unilever). Lastly, he has grant/research support from the Biotechnology and Biological Sciences Research Council. The other authors declare no competing interests.

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Halford, J., Boyland, E., Blundell, J. et al. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol 6, 255–269 (2010). https://doi.org/10.1038/nrendo.2010.19

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