It’s not clear why some people taking 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, a 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 taking GLP-1 drugs, possibly because they have a different fat distribution compared to men, or because their smaller average size could mean greater exposure to the drug.
And although GLP-1 drugs were initially 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 They have suggested Genetics, altered microbiomes and other medications that promote weight gain are all possible reasons for this. “A lot of it depends on the physiology and biology of each person. We can’t expect one medication to be one-size-fits-all,” says Amy Rothberg, an endocrinologist at the University of Michigan.
GLP-1 drugs cause weight loss by slowing the movement of food in the stomach and interacting with receptors in the brain to promote a feeling of fullness. Some people who take them report less “food rumbling” — they no longer have cravings or think about food all the time. As a result, they eat less. Patients start on a low dose that is gradually increased each week. Schmidt says some people may not respond to the lower doses, but eventually notice weight loss as the drug dose is increased.
Without lifestyle changes, these drugs are likely to be less effective for weight loss. Novo Nordisk, which makes Ozempic and Wegovy, and Eli Lilly, which makes Mounjaro and Zepbound, stress that the drugs are meant to be used alongside a healthy diet and exercise. In the semaglutide and tirzepatide trials, the drugs were combined with a low-calorie diet and increased physical activity. Clinical trials are often the best-case scenario when it comes to a drug’s effectiveness because they involve careful monitoring of participants and many follow-up visits with doctors. In real life, patients may not follow their weight-loss plan as diligently or see their doctor as regularly.
And while these drugs help reduce appetite, they don’t magically eliminate all temptations. After all, there is a significant social component to food consumption. “We may eat because it looks good, tastes good, we are in the company of others, or because it is available,” Rothberg says. A person who has those impulses or environmental stimuli competing with the drug will not lose as much weight as a person who doesn’t have to deal with those factors, he argues.
Differences in metabolism, or the way people break down food and convert it into energy, may also play a role. A person’s age and hormonal function, as well as the amount of physical activity they engage in, can all have an effect on metabolism.
Researchers are also studying whether genetic factors can explain some of the variability in response. In 2022, Pearson and colleagues published an article who identified a gene called ARRB1 which appears to be involved in glucose control. When they analyzed 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.
