The US Food and Drug Administration approved the medication Zepbound last week to treat chronic obesity. The injectable drug, made 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 medication called semaglutide that was also initially developed for diabetes treatment under the name Ozempic and has since been approved to treat obesity under the name Wegovy. Studies on both have shown high effectiveness in treating diabetes and obesity.
What is the difference between Zepbound and Wegovy? How do they work, 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 drugs that some internet pharmacies sell? And who should think about taking these drugs — and who shouldn’t?
To learn more about these medications, I spoke with CNN wellness medical 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: How do Zepbound and Wegovy differ? How do they work?
Dr. Leana Wen: Both are injection medications that are intended to be used once a week. They were both first approved to treat type 2 diabetes, and clinical trials also showed that they induced a significant amount of weight loss. Wegovy is already on the market, and Zepbound has just been approved by the FDA and is expected to be available later this year.
Both are in the class of drugs known as GLP-1 agonists. That means they mimic the digestive hormone glucagon-like peptide 1, or GLP-1, that is released by intestines when we eat. GLP-1 stimulates insulin production, which reduces blood glucose levels. The hormone also suppresses appetite and promotes the sensation of being full.
In addition to mimicking GLP-1, tirzepatide mimics another gut hormone called gastric inhibitory polypeptide, or GIP, that scientists believe has a similar effect on the body as GLP-1.
CNN: How well do these drugs work to reduce weight?
Wen: These medications both appear to work well. A March 2021 study on semaglutide, published in The New England Journal of Medicine, showed that people who took the medication lost an average of 14.9% of their body weight in about a year, compared with 2.4% in the placebo group. A September 2022 study, published in the journal JAMA Network Open, found that mean weight loss after six months was about 27 pounds (12.3 kilograms).
Tirzepatide also has excellent efficacy. A seminal July 2022 study in The New England Journal of Medicine found that those taking a lower dose of tirzepatide achieved an average weight reduction of 16%, or 35.5 pounds (16 kilograms), in about a year. Those taking a higher dose had a 21.4% reduction in body weight, or 49 pounds (22 kilograms). These are much larger reductions compared with the results for those who took a placebo, which achieved an average reduction of 2.4% or 5.3 pounds (2.4 kilograms).
CNN: Does that mean that tirzepatide works better than semaglutide?
Wen: The studies I mentioned were not done head-to-head, so I don’t think we can say that one medication works better than the other just yet. Like other medications, one may work better for some people compared with 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 a lifetime. If they are stopped, much of the weight loss is reversed.
In a way, this is no different than treatment for other chronic diseases such as high blood pressure, high cholesterol and diabetes. Not all patients will be willing or able to take these GLP-1 drugs for many years, though, and it’s important that studies are done to better understand how to help individuals who want to wean off them.
CNN: Is there a risk of side effects when taking GLP-1 medications?
Wen: Yes, there is. Many people experience gastrointestinal issues, such as nausea, diarrhea, vomiting and constipation. In rare cases, the medications have been associated with pancreas, gallbladder and stomach problems. Because tirzepatide and semaglutide are relatively newer therapeutics, long-term side effects are not known.
CNN: Should people consider more affordable versions of drugs that some internet pharmacies sell?
Wen: The safest thing is to buy medications that are directly made by the manufacturers, which are Eli Lilly for tirzepatide and Novo Nordisk for semaglutide. This requires a prescription from your health care provider and visiting a pharmacy to get the medications filled. Note that technically, the versions of the medicines someone needs for obesity treatment are Zepbound and Wegovy.
Physicians are also able to prescribe Mounjaro and Ozempic “off-label.” That means these drugs are approved to treat diabetes, but because the active ingredient (tirzepatide and semaglutide, respectively) is the same, they could be prescribed to people who need it for weight loss who don’t have diabetes.
In some cases, pharmacies may make their own versions of these drugs. This is a process called compounding, in which some specialized pharmacists can reformulate medications and sell them.
The FDA allows compounding under certain circumstances, including when the drug is in shortage, as is the case for both semaglutide and tirzepatide. However, unlike the manufacturer versions, compounded medications are not inspected by the FDA for quality, safety or effectiveness. The agency is clear that compounded medications are higher risk compared with ones directly made by manufacturers.
Then there is the matter of illegal internet pharmacies that are not approved to sell any medications. These rogue outfits should be avoided. The FDA has a resource for how to tell whether a website may be an illegal pharmacy that is distributing potentially unsafe medicines.
CNN: Who should think about taking these drugs — and who shouldn’t?
Wen: Obesity is a chronic medical condition. Individuals should take the medication, in consultation with their health care provider, 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, at or over 27. Zepbound is approved for those with BMI of 30 or over. Individuals are to use the medicines together with lifestyle changes including increased exercise and careful diet.
In general, 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 drugs, as there are for virtually all medications. Individuals should weigh the risks and benefits, as well as discuss alternatives, with their physicians.
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