Not everyone loses weight on Ozempic

It is not clear why some people who take these drugs lose a lot of weight while others lose none. “We still don’t understand most of the variation in response,” says Ewan Pearson, professor of diabetes medicine at the University of Dundee in Scotland. However, there are some known predictors of how patients will fare. For example, women tend to lose more weight than men with GLP-1 drugs, perhaps because they have a different distribution of fat compared to men, or because their smaller average size may mean higher exposure to the drug. .

And while GLP-1 drugs were originally approved as a diabetes treatment to improve blood sugar levels, they are less likely to produce significant weight loss in people with type 2 diabetes. Researchers have suggested genetics, altered microbiomes and other medications that promote weight gain as possible reasons for this. “A lot depends on a person’s physiology and biology. We can’t expect one drug to be right for everyone,” says Amy Rothberg, an endocrinologist at the University of Michigan.

GLP-1 drugs lead to weight loss by slowing the movement of food through the stomach and interacting with receptors in the brain to induce a feeling of satiety. Some people who take them report less “food cravings”—they no longer have cravings or think about food all the time. As a result, they eat less. Patients start with a low dose that is gradually increased each week. Schmidt says some people may not respond to lower doses, but eventually see weight loss as the medication is increased.

Without lifestyle changes, these medications are likely to be less effective for weight loss. Novo Nordisk, which makes Ozempic and Wegovy, and Eli Lilly, which makes Mounjaro and Zepbound, emphasize that the drugs are meant to be used in conjunction with a healthy diet and exercise. In the semaglutide and tirzepatide trials, the drugs were combined with a reduced-calorie diet and increased physical activity. Clinical trials are often the best case scenario when it comes to a drug’s efficacy because they involve careful tracking of participants and many follow-up visits with providers. In real life, patients may not follow their weight loss plan as diligently or see their doctor as regularly.

And while these drugs help curb appetite, they don’t magically eliminate all temptations. After all, there is a huge social component to eating food. “We may eat because it looks good, it tastes good, we’re in the company of others, or because it’s available,” says Rothberg. A person who has those environmental nudges or stimuli that compete with the drug won’t lose as much weight as the person who doesn’t have to deal with those factors, she argues.

Changes in metabolism, or how people break down food and convert it into energy, may also be at play. A person’s age and hormone function, as well as the amount of physical activity they perform, can affect metabolism.

Researchers are also examining whether genetic factors may explain some of the variability in response. In 2022, Pearson and his colleagues published a paper identifying a gene called ARRB1 which appears to be involved in glucose control. When they looked at genetic data from more than 4,500 adults, they found that people with certain variants in this gene have lower blood sugar levels while taking GLP-1 drugs.