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Science’s 2023 Breakthrough: GLP-1 Agonists Show Promise Against Obesity-Associated Disease

Originally developed to treat type 2 diabetes nearly 20 years ago, the excitement surrounding GLP-1 drugs to treat obesity has recently exploded.

This year, two landmark clinical trials showed that GLP-1 agonists produced meaningful health benefits beyond weight loss itself, Couzin-Frankel reports.

In August of this year, a trial of 529 people with obesity and heart failure found that after one year, people on the drug semaglutide — marketed in the United States as Ozempic for treating diabetes and Wegovy for obesity — had nearly double the heart improvement as measured on a standard heart failure questionnaire. Moreover, the results from another trial, published in November in show that among 17,000 people with excess weight and cardiovascular disease, those taking semaglutide had a 20% lower risk of heart attacks and strokes than those on placebo.

What's more, several trials are currently underway investigating the drugs' potential use in treating drug addictions, Alzheimer's and Parkinson's diseases.

"We choose our Breakthroughs based not just on the importance of the research but also their impacts across science and society as a whole," said Tim Appenzeller, the lead editor for Science's news section. "Our runners-up are all strong science. But none is as transformative in so many areas as the drugs we chose as our Breakthrough."

"And they are shaking up society, from global stock markets to popular culture, in ways that are not all positive," said Appenzeller.

As with most medical breakthroughs, the development and implementation of GLP-1 drugs isn't straightforward — there are growing unknowns and complexities concerning their safety, cost, equity and availability.

Right now, GLP-1 drugs cost roughly $1,000 per month and are assumed to require lifelong use to maintain their effectiveness. Some patients have reported serious gastrointestinal side effects, including pancreatitis and intestinal obstruction. Doctors also worry about people who aren't obese or significantly overweight resorting to their use to quickly slim down.

"In honoring these therapies, we also acknowledge the uncertainties, even anxieties, this sea change brings," Couzin-Frankel writes.

"But for all their promise, GLP-1 agonists have raised more questions than they have answered," writes Science Editor-in-Chief Holden Thorp in a related Editorial.

According to Thorp, these therapies and the science underlying their discovery and development are forcing important discussions about the way obesity is considered.

"Old pejorative tropes about obesity being the result of low willpower were hurtful to begin with, but now there is compelling evidence that a biochemical difference, not mental weakness, is responsible for weight gain," writes Thorp.

As more focused research into obesity continues, driven in part by the emerging successes of GLP-1 drugs, understanding and perceptions of obesity may change to recognize obesity as a chronic illness rooted in biological and environmental factors.

"That might lower the stigma and judgement around weight," writes Thorp. "And that would truly be a breakthrough."

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