1814 lipase inhibitor drug orlistat, the development of new lipase inhibitor cetilistat seems to be one of the least risky. Other approaches, such as MTP inhibition, need further proof of principle. The value of other potential targets in the battle against obesity, including 11β-HSD1, SIRT 1, TGR 5 and the modulation of intestinal flora, will become clear during the coming few years. Combination therapies, possibly including drug-food combinations, not only offer the advantage of multi-target therapy with sometimes higher efficacy, but may also reduce side effects and risks. In particular, for the preparations acting within the CNS, the coming years will be crucial to see whether side effects remain acceptable. Looking at the history of weight loss drugs, it is understandable that authorities will be watchful. Obesity is not regarded as a life-threatening disease, and, if effective, anti-obesity drugs will be prescribed to a large and diverse group of people. Furthermore, considerable off- label use and distribution via the Internet and other channels is to be expected. Given the high activity in this field of research and notwithstanding the possible risks for failures, it seems obvious that the therapeutic arsenal of weight management drugs and other compounds used in obesity will change considerably in the coming five years. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial Li- cense which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. REFERENCES 1. Bessesen DH. Update on obesity. J Clin Endocrinol Metab. 2008;93:2027–34. 2. James WPT. The epidemiology of obesity: the size of the problem. J Intern Med. 2008;263:336–52. 3. Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity. 2008;16:2323–30. 4. Despres J-P, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881–7. 5. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735–52. 6. Haslam DW, James WP. Obesity. Lancet. 2005;366:1197–209. 7. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the framingham heart study. Circula- tion. 2007;116:39–48. 8. Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all-cause mortality in men. Obesity. 2006;14:336–41. 9. Behn A, Ur E. The obesity epidemic and its cardiovascular consequences. Curr Opin Cardiol. 2006;21:353–60. Witkamp 10. Han TS, Sattar N, Lean M. Assessment of obesity and its clinical implications. Br Med J. 2006;333:695–8. 11. O’Donovan G, Thomas EL, McCarthy JP, et al. Fat distribution in men of different waist girth, fitness level and exercise habit. Int J Obes. 2009;33:1356–62. 12. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010;31:737–46. 13. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7. 14. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132:2169–80. 15. Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–77. 16. Mittra S, Bansal VS, Bhatnagar PK. From a glucocentric to a lipocentric approach towards metabolic syndrome. Drug Discov Today. 2008;13:211–8. 17. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diab Care. 2008;31:289–94. 18. Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol. 2008;8:923–34. 19. Shoelson SE, Goldfine AB. Getting away from glucose: fanning the flames of obesity-induced inflammation. Nat Med. 2009;15:373–4. 20. Nedungadi TP, Clegg DJ. Sexual dimorphism in body fat distribution and risk for cardiovascular diseases. J Cardiovasc Transl Res. 2009;2:321–7. 21. Rebuffe-Scrive M, Andersson B, Olbe L, Bjorntorp P. Metab- olism of adipose tissue in intraabdominal depots of nonobese men and women. Metabolism. 1989;38:453–8. 22. McLaughlin TM, Liu T, Yee G, et al. Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue. Obesity. 2010;18:926–31. 23. Janiszewski PM, Ross R. The utility of physical activity in the management of global cardiometabolic risk. Obesity. 2009;17. 24. Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50:1105–12. 25. Ross R, Bradshaw AJ. The future of obesity reduction: beyond weight loss. Nat Rev Endocrinol. 2009;5:319–26. 26. Goodyear LJ. The exercise pill - too good to be true? N Engl J Med. 2008;359:1842–4. 27. Himms-Hagen J. Exercise in a pill: feasibility of energy expenditure targets. Curr Drug Targets CNS Neurol Disord. 2004;3:389–409. 28. Narkar VA. AMPK and PPARδ agonists are exercise mimetics. Cell. 2008;134:405–15. 29. Berridge KC, Ho CY, Richard JM, DiFeliceantonio AG. The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders. Brain Res. 2010. 30. Halford JCG, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol. 2010;6:255–69. 31. Mela DJ. Eating for pleasure or just wanting to eat? Reconsider- ing sensory hedonic responses as a driver of obesity. Appetite. 2006;47:10–7. 32. Adan RAH, Vanderschuren LJMJ, la Fleur SE. Anti-obesity drugs and neural circuits of feeding. Trends Pharmacol Sci. 2008;29:208–17. 33. Cota D, Tschöp MH, Horvath TL, Levine AS. Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res Rev. 2006;51:85–107. 34. Bult MJF, van Dalen T, Muller AF. Surgical treatment of obesity. Eur J Endocrinol. 2008;158:135–45.