An Historical Review of Steps and Missteps in the Discovery of

The epidemic of obesity cries out for strategies to prevent it, and for treatment when prevention fails. Yet despite the obvious need, the path to developing anti-obesity medications is strewn with failures. This review examines some historical developments in the management of obesity prior to the 20th century followed by more recent efforts to find a “cure.” Since obesity has been a human disease since paleolithic times, discussion of treatment prior to the scientific revolution in about 1500 CE will include comments on treatment of obesity in Grecian Medicine and the Treatment of Sancho “The Fat” King of Leon in 10th century northern Spain. We will then trace treatment trends through time, ending in the early 21st century. In the first half of the 20th century there were 3 main themes associated with drug treatment of obesity: use of thyroid hormones, the interlude with dinitrophenol as drug regulation was beginning to expand, and the introduction of amphetamines and Rainbow Pills. In the second half of the 20th century many new treatment approaches were explored as the scientific basis for understanding regulation of food intake expanded, particularly after the discovery of leptin in 1994. The fact that amphetamine could be addictive led to the search for compounds that acted in the central nervous system with retained the anorectic properties but were not addictive. Both anti-depressant and anticonvulsive drugs were evaluated with disappointing results. The idea of enhancing energy expenditure with thermogenic drugs was pursued but led to a dead end. Peptides, metabolic drugs and drugs that act on the gastrointestinal track are currently under exploration. This chapter makes an effort to answer the question of why it has been so difficult to develop effective medications for the management of obesity. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

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