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Medicines such as Ozempic and Wegovy have achieved blockbuster status due to their effectiveness promoting weight loss. These drugs mimic the activity of GLP-1, a natural hormone that is released after eating. Originally developed for type 2 diabetes, this drug class is now offering new hope to individuals who have struggled unsuccessfully to control their weight through diet and exercise. Jeffrey Friedman, a physician-scientist at The Rockefeller University, sees the new weight loss drugs as both a medical milestone and a dramatic turning point in the quest to understand the causes of obesity. Dr. Friedman, a recipient of the Albert Lasker Award, the Breakthrough Prize, and many other honors, is an innovator in research on metabolism. In the mid-1990s, he and his colleagues isolated an obesity-related gene and showed that it encoded a previously unknown hormone, dubbed leptin, that plays a key role in controlling appetite, energy expenditure, and fat storage. The discovery of leptin provided compelling evidence of a genetic contribution to obesity and established a model for chemical signaling between the digestive tract and the brain that continues to inform basic research and drug discovery related to obesity.