Understand how Zepbound, a new medication for obesity, works; expert explains


Photo: Disclosure/Eli Lilly.

The US Food and Drug Administration (FDA) approved the drug Zepbound last week to treat chronic obesity. The injectable medication, manufactured by the pharmaceutical company Eli Lilly, has the active ingredient tirzepatide, which had been approved in May 2022 to treat type 2 diabetes under the name Mounjaro.

Tirzepatide joins a similar drug called semaglutide, which was also initially developed to treat diabetes under the name Ozempic and has since been approved to treat obesity and is called Wegovy. Studies on both have demonstrated high efficacy in treating diabetes and obesity.

What is the difference between Zepbound and Wegovy? How and how well do they work? How long do they need to be used? What are the possible side effects? Should people consider more affordable versions of medications sold by some online pharmacies? And who should consider taking these medications – and who shouldn’t?

To learn more about these medications, I spoke with CNN’s medical wellness expert, Dr. Leana Wen. Wen is an emergency physician and professor of health policy and management at the George Washington University Milken Institute School of Public Health. She previously served as Baltimore’s health commissioner.

CNN: What is the difference between Zepbound and Wegovy? How do they work?

Dr. Leana Wen: Both are injectable medications that should be used once a week. Both were first approved to treat type 2 diabetes, and clinical trials also showed they induced significant weight loss. Wegovy is already on the market and Zepbound has just been approved by the FDA and should be available later this year.

Both are in the class of medications known as GLP-1 agonists. This means they mimic the digestive hormone glucagon-like peptide 1, or GLP-1, which is released from the intestines when we eat. GLP-1 stimulates insulin production, which reduces blood glucose levels. The hormone also suppresses appetite and promotes feelings of satiety.

In addition to mimicking GLP-1, tirzepatide mimics another gut hormone called gastric inhibitory polypeptide, or GIP, which scientists believe has a similar effect on the body as GLP-1.

CNN: How well do these medications work to reduce weight?

Wen: Both medications seem to work well. A March 2021 study of semaglutide, published in The New England Journal of Medicine, showed that people taking the drug lost an average of 14.9% of their body weight over about a year, compared with 2.4% in placebo group.

A September 2022 study published in the journal JAMA Network Open found that the average weight loss after six months was about 12.3 pounds.

Tirzepatide also has excellent efficacy. A seminal July 2022 study published in The New England Journal of Medicine found that those who took a lower dose of tirzepatide achieved an average weight reduction of 16%, or 16 pounds, in about a year.

Those who took a higher dose had a 21.4% reduction in body weight, or 22 kg. These are much greater reductions compared to the results of those taking placebo, who achieved an average reduction of 2.4% or 2.4 pounds.

CNN: Does this mean tirzepatide works better than semaglutide?

Wen: The studies I mentioned weren’t done head-to-head, so I don’t think we can say that one drug works better than the other yet. Like other medications, one may work better for some people than another.

CNN: How long do these medications need to be taken?

Wen: At the moment, the understanding is that tirzepatide and semaglutide need to be taken for life. If they are stopped, much of the weight loss will be reversed.

In some ways, this is no different than treating other chronic diseases, such as high blood pressure, high cholesterol, and diabetes. However, not all patients will be willing or able to take these GLP-1 medications for many years, and it is important that studies be done to better understand how to help individuals who wish to come off them.

CNN: Is there a risk of side effects when taking GLP-1 medications?

Wen: Yes, there is. Many people experience gastrointestinal problems, such as nausea, diarrhea, vomiting and constipation. In rare cases, the medications have been linked to pancreas, gallbladder, and stomach problems. As tirzepatide and semaglutide are relatively newer therapies, long-term side effects are not known.

CNN: Should people consider more affordable versions of medications sold by some online pharmacies?

Wen: The safest thing is to buy medicines manufactured directly by the manufacturers, which are Eli Lilly for tirzepatide and Novo Nordisk for semaglutide. This requires a prescription from your doctor and a visit to a pharmacy to obtain the medications. Note that technically, the versions of the drugs needed to treat obesity are Zepbound and Wegovy.

Doctors may also prescribe Mounjaro and Ozempic “off-label.” This means that these medications are approved to treat diabetes, but because the active ingredient (tirzepatide and semaglutide, respectively) is the same, they can be prescribed to people who need them for weight loss and who do not have diabetes.

Ozempic has the active ingredient semaglutide which also treats obesity / Florian Gaertner/Photothek via Getty Images

In some cases, pharmacies may manufacture their own versions of these medications. This is a process called manipulation, in which some specialized pharmacists can reformulate medicines and sell them.

The FDA allows manipulation in certain circumstances, including when the drug is in short supply, as is the case with semaglutide and tirzepatide. However, unlike manufacturer versions, compounded medications are not inspected by the FDA for quality, safety, or effectiveness. The agency makes it clear that compounded medicines present a greater risk compared to those manufactured directly by manufacturers.

Then there is the issue of illegal pharmacies on the internet that are not approved to sell any medications. They are dishonest and should be avoided. The FDA has a resource to find out if a website could be an illegal pharmacy that distributes potentially dangerous medications.

CNN: Who should consider taking these medications – and who shouldn’t?

Wen: Obesity is a chronic medical condition. Individuals should take medication, in consultation with their doctor, if they have this condition – not if they are simply unhappy with their appearance and trying to lose a few pounds.

For Wegovy, patients are eligible if they have a body mass index, or BMI, of 27 or greater. Zepbound is approved for those with a BMI of 30 or greater. Individuals must use the medications along with changes in style lifestyle, including increased physical exercise and careful diet.

Overall, I think it’s a good thing that there are new tools available for patients with obesity, which increases the risk of heart disease, diabetes, many forms of cancer, and early death. There are potential side effects and risks associated with these medications, as there are with virtually all medications. Individuals should weigh the risks and benefits, as well as discuss alternatives, with their doctors.


The article is in Portuguese

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