Why Ozempic Isn't Working For You, According To Experts

About 10% to 15% of people struggle to lose weight while taking popular GLP-1 medications like Ozempic and Wegovy, according to the Washington Post. These individuals are often labeled non-responders because they typically lose less than the standard 5% benchmark. By contrast, people who respond well to these medications may lose anywhere from 15% to over 20% of their total body weight over roughly a year and a half, according to WebMD. So, why do some people have trouble losing weight on GLP-1 medications?

Genetics and GLP-1 receptors can block weight loss progress on GLP-1 weight loss medication.

There are several reasons why someone may not lose weight on GLP-1 medications. Factors such as genetics, metabolic rate (how efficiently the body converts food into energy), and overall health all play a role. Research also suggests that differences in how the body activates GLP-1R and GIPR receptors, which are essential for regulating glucose metabolism and energy balance, may make weight loss more difficult for some individuals. The effectiveness of these receptors varies from person to person, which can influence how someone responds to medications like Ozempic or  Zepbound.

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For example, in people with Type 2 diabetes or chronic obesity, receptor expression or responsiveness may be reduced compared to healthy individuals. Research has found that people who carry a specific variant in the GLP1R gene (rs10305420) tend to lose significantly more weight than non-carriers. However, this same variant is also associated with a higher likelihood of side effects, particularly nausea and vomiting, The Washington Post notes. But there’s a trade-off. Studies show that individuals with one copy of the GLP1R variant lost an average of 1.7 pounds more over eight months than those without it, while those with two copies lost 3 pounds more.

Hormonal changes and nutrition can also play a factor.

Other factors can also interfere with weight loss. According to GoodRx, hormonal changes can make it harder to shed pounds while taking GLP-1 medications. These changes may be linked to menopause, postpartum hormonal shifts, or thyroid disorders.

Most people experience a reduced appetite on medications like Ozempic and Wegovy, but that is not always enough to ensure weight loss. Some individuals may still consume more calories than their body needs.

“There’s a small group of people who eat for emotional reasons, or reasons unrelated to hunger cues,” said Dr. Sonal Chaudry, a board-certified endocrinologist and assistant professor in the Division of Endocrinology, Diabetes and Metabolism at New York University. “Others may also continue to eat even if they feel physically full.”

Not losing weight on GLP-1 medications is also common early in treatment. This can happen when someone is still on a low starting dose, hasn’t been on the medication long enough for it to fully take effect, or needs to make additional lifestyle changes. Other contributing factors may include gradual dose increases, poor nutrition, lack of physical activity, or hitting a natural plateau.

Ultimately, if you are having trouble losing weight on GLP-1 medications, it is best to speak with your doctor to determine the most effective approach for your individual situation.

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