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everyone loses weight on Ozimpic. For

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many patients, GLP-1 drugs like Ozimpic and

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Wigovii lead to substantial weight loss, but

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some seem much less benefit and researchers

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are trying to figure out why. By

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Emily Mowen. Danielle

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Rosas had tried all the usual

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avenues to lose weight, modifying her

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diet, increasing her exercise, but the

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weight always came back. In

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2020, she turned to Ozimpic. She

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was 225 pounds at the time. My

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weight has fluctuated a lot throughout my adulthood,

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says Rosas, now 36. After

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three months of injecting the drug once a week, she'd

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lost about 5% of her body

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weight, around 5 pounds. She was

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disappointed. She had hoped to lose

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more in trials patients had lost. the

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drugs are meant to be used alongside a

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healthy diet and exercise. In

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trials of samaglitide and terzepatide, the

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medications were paired with a reduced

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calorie diet and increased physical activity.

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Clinical trials are often the best-case scenario

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when it comes to a drug's efficacy

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because they involve careful tracking of participants

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and many follow-up visits with providers. In

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real life, patients may not follow their

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weight loss plan as diligently or see

6:26

their doctors regularly. And

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while these drugs help curb appetite, they

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don't magically eliminate all temptations. After

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all, there is a major social component to eating

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food. We may eat because it

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looks good, tastes good. We're in the company of

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others or because it's available, Rothberg says. A

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person who has those environmental pushes or stimuli

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competing with the drug won't lose as much

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weight as the person who doesn't have to

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deal with those factors, she argues. Differences

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in metabolism or how people break down

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food and convert it into energy could

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also be at play. A person's age

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and hormone function, as well as the

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amount of physical activity they get, can

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have an effect on metabolism. Researchers

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are also looking into whether genetic factors may

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explain some of the variability in response. In

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2022, Pearson and his colleagues published a

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paper that identified a gene called ARRB1

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that seems to be involved in glucose

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control. When they looked at genetic data

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from more than 4,500 adults, they

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found that people with certain variants in

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this gene have lower blood sugar levels

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while taking GLP1 drugs. The

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ARRB1 gene is involved in recycling the

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GLP1 receptor within the cell and returning

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it to the cell's surface. It's

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likely, Pearson says, that people with these

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variants, about 2-3% of the white population

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and 11% of Hispanics, have more

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of these receptors in their insulin-making

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pancreatic cells. As

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GLP1 drugs work by binding to

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these receptors, the bigger reduction in

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blood sugar may be explained by

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greater binding activity spurring more insulin

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production. But in Pearson's

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study, the genetic alterations weren't connected

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with weight loss, meaning the effect

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was probably limited to the pancreas.

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Even so, it means that there are likely

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to be genetic factors that account for some

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of the weight loss response, and it may

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be that variants in multiple genes rather than

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just one drive people's different responses. Pearson's

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group is now working with researchers at

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the University of Montreal to study genetic

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factors in weight loss in people on

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GLP1 drugs. For

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GLP1 non-responders, it could be that

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another mechanism is involved in their

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obesity, says Rekha Kumar, an endocrinologist

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and chief medical officer at Found,

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a company that provides personalized weight

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loss plans. It's possible that

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whatever drove them to gain weight isn't

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necessarily related to the GLP1 pathway, she

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says. They may do better

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on medicine that works differently. Researchers

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at the Mayo Clinic are trying to

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categorize people based on their obesity phenotype

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or the behavioral components behind the disease.

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Mayo gastroenterologist Andrew Acosta and his

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colleagues have used machine learning methods

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to describe four major types of

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obesity. Hungry brain, in which

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people never feel full. Hungry gut, where

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people eat until they are full but

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feel hungry again soon after. Emotional

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hungry, which are people who eat to

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cope with emotional issues or to reward

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themselves regardless of whether they're hungry. And

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slow burn, people who don't burn calories

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fast enough. Research by Acosta

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has shown that people with the hungry gut

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type lose more weight on GLP1 drugs than

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the other types. Non-responders

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may not have to wait for other

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options. GLP1 drugs seem to be getting

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more effective, whereas samaglitide

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targets just the GLP1 receptor.

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The newer terzepatide targets GLP1

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plus another receptor, GIP. Drugmakers

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are studying whether new drugs that target

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more than one receptor involved in obesity

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could boost weight loss. As

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we get more sophisticated with these gut

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hormone combinations, I think we'll be

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able to see more responsiveness in the population.