Chapter 16. Progress in the Development of Antiobesity Drugs

Publisher Summary Novel pharmacological approaches include, in particular, reducing the availability of dietary carbohydrate or lipid by altering the intestinal absorption and modifying lipid metabolism. These function by modulating peripheral energy metabolism and have received increasing attention throughout the world. Recent double-blind studies have demonstrated the superiority of sustained-release fenfluramine over the rapid-release form or placebo as an adjunct to diet restriction in effecting the weight loss in obese patients. Improved glucose tolerance and insulin responsei5 and significant decreases in serum cholesterol and triglycerides were observed. Studies in man, monkeys, and rats show that fenfluramine was metabolized to at least four compounds with pharmacological activity, d- and I-fenfluramine, and d- and I-norfenfluramine. Retardation or inhibition of digestion of dietary carbohydrate should lead to a dimunition of hyperglycemia and hyperinsulinemia in subjects suffering from obesity or diabetes. In a series of linked aryl aryloxypropanolamines synthesized with the aim of identifying compounds that would reduce body weight by decreasing body fat without affecting appetite, significantly suppressed body weight in rats and dogs. The compound, however, possessed considerable hematological toxicity. Results from a study in healthy volunteers suggested that a dose of 100-200 mg of Bay g 5421 per meal might be effective for clinical trials in diabetes, hypertriglyceridemia, and obesity.