It’s not clear why some people lose a lot of weight when they take these drugs, while others don’t lose any at all. “Most of the differences in response are still unknown,” says Euan Pearson, professor of diabetes medicine at the University of Dundee in Scotland. But there are some known factors that predict how patients will fare. For example, women tend to lose more weight than men when they take GLP-1 drugs, possibly because women’s fat distribution is different to men’s, or because women’s smaller average size gives them greater exposure to the drug.
GLP-1 drugs were initially approved as diabetes treatments to improve blood sugar levels, but people with type 2 diabetes can’t expect significant weight loss. Researchers suggest that genetics, changes in the microbiome, and other medications that promote weight gain may be to blame. “It really depends on an individual’s physiology and biology,” says Amy Rothberg, an endocrinologist at the University of Michigan. “You can’t expect a drug to be one size fits all for everyone.”
GLP-1 drugs slow the movement of food through the stomach and interact with receptors in the brain to promote feelings of fullness, which can lead to weight loss. Some people report a reduction in “food noise” — that is, they no longer have food cravings and are no longer constantly thinking about food. As a result, they eat less. Patients start on a low dose and gradually increase it each week. Schmidt says that low doses don’t work for some people, but as people increase the amount of medication, they eventually lose weight.
Without lifestyle changes, these drugs are likely to be less effective at reducing weight. Novo Nordisk, which makes Ozempic and Vigovi, and Eli Lilly, which makes Maunjaro and Zepbound, emphasize that these drugs should be used in conjunction with a healthy diet and exercise. In the semaglutide and tirzepatide trials, the drugs were combined with a calorie-restricted diet and increased physical activity. Clinical trials often represent the best-case scenario for a drug’s effectiveness, because they involve careful tracking of participants and many follow-up visits by health care providers. In real life, patients may not follow weight-loss plans as diligently or visit their doctors as regularly.
While these medications help curb appetite, they don’t magically eliminate all temptation. After all, there’s a large social component to eating food. “We may eat it because it looks good, tastes good, we’re with other people, or it’s available,” says Rothberg. People who have environmental pressures and cues that compete with their medication won’t lose weight as much as those who don’t have to deal with those factors, she argues.
Differences in metabolism, or how we break down food and turn it into energy, may also play a role. A person’s age, hormone function and amount of physical activity can affect metabolism.
Researchers are also investigating whether genetic factors could explain some of the variability in responses. In 2022, Pearson and his colleagues published ARRB1 This gene is thought to be involved in blood sugar control. By examining the genetic data of more than 4,500 adults, the researchers found that people with certain mutations in this gene had lower blood sugar levels while taking GLP-1 drugs.
