When Jessica Layeux, a cybersecurity expert from Monticello, Minn., started taking the weight-loss drug Zepbound last year, she didn’t have any of the side effects she had heard about. She didn’t feel much of a change in her hunger or cravings either.. At first, Ms. Layeux, 42, was optimistic that she would see results as she moved to a higher dose. But as the months went on with almost no weight loss, Ms. Layeux started to blame herself. She began obsessing over whether she was storing the drug at the right temperature or injecting it into the right place. At doctors appointments, she would rush to share that she was eating healthy and exercising, so that her provider wouldn’t think it was her fault.. Over 15 months on Zepbound, Ms. Layeux lost only a pound or two. “No matter what I do, these ‘miracle drugs’ don’t work,” she said.. GLP-1 drugs like Zepbound have helped millions of people shed significant weight. But then there are the often-overlooked outliers: In clinical trials, about one in 10 people on the drugs were “non-responders,” losing less than 5 percent of their body weight, compared with the average of 15 to 21 percent. With so much attention on the benefits of these drugs, the experiences of non-responders are often overlooked.. For these patients, it can be maddening to see no weight loss after months of treatment and thousands of dollars spent.. “It felt extremely defeating,” said Ms. Layeux.. Scientists aren’t sure why some people lose so little weight and why others lose a tremendous amount. But it’s a question they are now trying to answer, looking to genetics and other patient characteristics to predict how someone will respond.. Genetics, hormones, and other factors. One promising theory suggests that genetics plays a role, said Marie Spreckley, a researcher at the University of Cambridge.. Story continues below this ad. Genetics can influence hunger levels, fullness and metabolism, or how the body bums energy. Scientists increasingly think that each of these factors contributes to whether someone develops obesity and how someone might respond to weight-loss drugs.. Semaglutide and tirzepatide, the compounds in the two most popular weight-loss medications, largely work by dialing down appetite and silencing “food noise.” That means people whose obesity is unrelated to food intake might see less of an effect on these drugs, said Dr. Amy Sheer, an obesity medicine doctor at University of of Cambridge.. Genetics can influence hunger levels, fullness and metabolism, or how the body bums energy. Scientists increasingly think that each of these factors contributes to whether someone develops obesity and how someone might respond to weight-loss drugs.. Semaglutide and tirzepatide, the compounds in the two most popular weight-loss medications, largely work by dialling down appetite and silencing “food noise.” That means people whose obesity is unrelated to food intake might see less of an effect o
