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

Despite their widespread and growing use, GLP-1 receptor agonist drugs were by no means an overnight success – decades of developments, unexpected discoveries, and some notable failures all paved the way to the 2023 Breakthrough of the Year. | Science/AAAS

Science has named the development of glucagon like peptide-1 (GLP-1) agonists — and this year's discovery that these drugs can blunt obesity-associated health problems — as its 2023 Breakthrough of the Year.

Obesity is a cause of global health concern. Although the causes of obesity span myriad genetic, physiological, environmental and social factors, risks of obesity-related medical problems can be life-threatening and include heart disease, diabetes, arthritis, liver disease and certain cancers.

For many, the condition can exact a tremendous toll on mental well-being due to the caustic social stigmas associated with being overweight.

Drug treatments for obesity have had "a sorry past, one often intertwined with social pressure to lose weight and the widespread belief that excess weight reflects weak willpower," writes Jennifer Couzin-Frankel in the Breakthrough news feature, published in the Dec. 15 issue of Science. 

However, a new class of drug therapies for weight loss has emerged and is showing promising results — and challenging outdated notions about obesity.

Shaking up Science and Society

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."

Runners-up and Breakdowns

Runners-up for the Science Breakthrough of The Year include advancements in antibody therapies that may slow neurodegeneration in the brains of people with Alzheimer's disease; the discovery of natural hydrogen sources below the Earth's surface; the push for systemic changes in how early-career scientists are treated at institutions worldwide; strong evidence that humans arrived in the Americas thousands of years earlier than most archaeologists had thought; findings that show Earth's crucial carbon pump is slowing down; interstellar signals from massive black hole mergers; the development of AI-assisted weather forecasting; new malaria vaccines; and the deployment of exascale computing, which promises to bring unprecedented computational power to many fields of science.

Science also named several "breakdowns" of the year. They include several emerging troubles for the U.S. Antarctic Program; continued political discord and distrust about COVID-19's origin, the false claim of room-temperature superconductivity; and the precipitous decline of the social media platform X, formerly known as Twitter.

[credit for Science cover illustration: Stephan Schmitz/Folioart]