1810 Fig. 14 Structures of some β3— adrenergic agonists investigated as anti-obesity compounds. Witkamp syndrome (145). However, more studies are needed to determine the therapeutic potential of this class, and there appear to be no compounds having progressed beyond phase I clinical trials at the moment (146). Growth Hormone (GH) Analogues The concept of using GH or its analogues to combat obesity dates back several years. It was based on different principles, including lower GH levels and a reduced responsiveness to GH in obese persons, which is generally restored after weight loss (111). However, when combined with a hypocaloric diet, GH was not shown to have additional benefits. In combination with an isoenergetic diet, GH induced only a modest reduction in weight as compared with placebo. Furthermore, several studies reported a worsening of insulin resistance in subjects treated with GH. A modified fragment of human GH, AOD9604, has been in development for weight management. It had been designed to mimic the lipolytic effects of GH without producing growth effects. However, its development was stopped in 2007 because of insufficient efficacy during a 24- week trial with 536 subjects. Taken together, there seems to be little enthusiasm left for GH as a target to reduce body weight. Inhibition of 11-Β Hydroxysteroid Dehydrogenase Type 1 The 11-β hydroxysteroid dehydrogenase enzymes type 1 isoform (11β-HSD1) is currently receiving considerable attention because of its possible role in the development of the metabolic syndrome (148–152). This is amongst others based on the observation that overlap exists in patho-physiology and symptomology between Cushing syndrome and the metabolic complications of visceral obesity. The enzyme 11β-HSD1 primarily catalyzes the reduction of hormonally inactive cortisone into the high-