Obesity plays out as a private struggle and a public health crisis. In the United States, about 70% of adults are affected by excess weight, and in Europe that percentage is more than half. The stigma against fat can be crushing; its risks, life-threatening. Defined as a body mass index of at least 30, obesity is thought to power type 2 diabetes, heart disease, arthritis, fatty liver disease, and certain cancers. Yet drug treatments for obesity have a sorry past, one often intertwined with social pressure to lose weight and the widespread belief that excess weight reflects weak willpower. From “rainbow diet pills” packed with amphetamines and diuretics that were marketed to women beginning in the 1940s, to the 1990s rise and fall of fen-phen, which triggered catastrophic heart and lung conditions, history is beset by failures to find safe, successful weight-loss drugs. But now, a new class of therapies is breaking the mold, and there’s a groundswell of hope that they may dent rates of obesity and interlinked chronic diseases. The drugs mimic a gut hormone called glucagon-like peptide-1 (GLP-1), and they are reshaping medicine, popular culture, and even global stock markets in ways both electrifying and discomfiting. Originally developed for diabetes, these GLP-1 receptor agonists induce significant weight loss, with mostly manageable side effects. This year, clinical trials found that they also cut symptoms of heart failure and the risk of heart attacks and strokes, the most compelling evidence yet that the drugs have major benefits beyond weight loss itself. For these reasons, Science has named GLP-1 drugs the Breakthrough of the Year.
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