Science’s 2023 Breakthrough of the Year: GLP-1 agonists show promise for obesity-associated health problems

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. Although obesity’s causes span genetic, physiological, environmental, and social factors, as a medical problem, obesity’s risks can be life-threatening – including heart disease, diabetes, arthritis, liver disease, and certain cancers. 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. However, a new class of drug therapies for weight loss has emerged and is showing promising results. Originally developed to treat diabetes nearly 20 years ago, the excitement surrounding GLP-1 drugs to treat obesity has recently exploded. And this year, two landmark clinical trials that showed in large numbers that GLP-1 agonists produced meaningful health benefits beyond weight loss itself. What’s more, several trials are currently underway investigating their use in treating drug addiction, Alzheimer’s, and Parkinson’s diseases. “But for all their promise, GLP-1 agonists have raised more questions than they have answered – a hallmark of a true breakthrough,” writes Science journals’ editor-in-chief, Holden Thorp, in a related Editorial. “We recognize… that obesity comes with medical and social complexities,” writes Couzin-Frankel. Both her story and the related editorial highlight how the development and implementation of these drugs are forcing important discussions about the way obesity is considered, which might help lower the stigma and judgment around weight. Couzin-Frankel’s story also highlights concerns about the drugs’ cost, availability, associated side effects, and their potential need to be taken indefinitely. Doctors also worry about people who aren’t obese or overweight resorting to their use to quickly slim down.

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; the confirmation of the deep antiquity of human footprints discovered in an ancient lake in New Mexico; 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.