J. Endocrinol. Invest. 25: 905-914, 2002 REVIEW ARTICLE New pharmacological tools for obesity E. Nisoli, and M.a. Carruba Center for Study and Research on Obesity, University of Milan, Department of Preclinical Sciences, LlT A Vialba, L. Sacco Hospital, and Istituto Auxologico Italiano, Milan, Italy ABSTRACT. Obesity is a multi-factorial, chronic disorder that has reached epidemic proportions in most industrialized countries and is threaten- ing to become agiobai epidemic. Obese patients are at a higher risk from coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, certain cancers, cerebrovascular accidents, os- teoarthritis, restrictive pulmonary disease, and sleep apnea. Obesity is a particularly challeng- ing clinical condition to treat, because of its com- plex pathophysiological basis. Indeed, body weight represents the integration of many bio- INTRODUCTION Obesity is a multi-factorial, chronic disorder that has reached epidemie proportions in most industrialized countries and is threatening to become a global epi- demie (1). Despite public health efforts, no marked shift towards healthier lifestyles is likely over the next 10 yr; rather, the health problems of obese and over- weight people will increase. The number of obese adults in the 7 major markets (United States, France, Germany, Italy, Spain, United Kingdom and Japan) is expected to grow from 95 million in 2000 to 139 mil- lion in 2010. Less than 25% of potential patients are formally diagnosed as obese, and less than 20% of those who are diagnosed are treated with pharma- cological therapies. The risk of morbidity and mortality increases with an increase in bw beyond a BMI (weight in kg/height in m 2 ) of 27 and with an increase in waist circumference (as an index of visceral localization of fat). Obese pa- tients are at higher risk from coronary artery disease, Key-words: Obesity. anti-obesity drugs, metabolie fitness, obesity-relat- ed disorders. Correspondenee: Prof. Enzo Nisoli, Centro di Studio e Rieerea sull'Obe- sita, Dipartimento di Seienze Preeliniehe LIlA, Vialba, Ospedale L. Saeeo, Via G.ß. Grassi 74, 20157 Milano, Italia. E-mai!: enzo.nisoli@unimi.it Aeeepted September 10, 2002. 905 logical and environmental components. Efforts to develop innovative anti-obesity drugs have been recently intensified. In broad terms, re- searchers use different distinct strategies: first, to reduce energy intake; second, to increase en- ergy expenditure; third, to alter the partitioning of nutrients between fat and lean tissue. In the present review we concentrate on the first of these strategies, by underlining the new phar- macological tools wh ich are presently studied. (J. Endocrinol. Invest. 25: 905-914,2002) ©2002, Editrice Kurtis hypertension, hyperlipidemia, diabetes mellitus, cer- tain cancers, cerebrovascular accidents, osteoarthri- tis, restrictive pulmonary disease, and sleep apnea (2). Recently, a great debate has weighed these risks, because not all studies show that being slightly over- weight carries an increased risk of mortality in young persons (3) and because, even if one maintains weight loss, there are no clinical studies demon- strating long-term maintenance of weight loss and thus, the long-term reduction of cardiovascular risk factors has not been assessed. Nevertheless, Wil- liamson et al. (4) reported that the association be- tween intentional weight loss and longevity in mid- dle-aged overweight women appears to depend on their health status: in women with obesity-related health conditions (no, = 15,069), intentional weight loss of any amount was associated with a 20% re- duction in all-cause mortality, primarily due to a 40- 50% reduction in mortality from obesity-related can- cers; in women with no pre-existing illness (no,=28,388), intentional weight loss of kg that occurred within the previous year was associated with an approximate 25% reduction in all-cause, car- diovascular, and cancer mortality; however, loss of <9.1 kg or loss that occurred over an interva I of yr was generally associated with small to modest in- creases in mortality. There is, however, no conclu- sive evidence that intentional weight loss in obese people without obvious comorbidities is beneficial,