Jenny Niwa
You have probably heard about several very popular new weight loss drugs, such as Wegovy, Ozempic, Mounjaro, and Zepbound. Although Ozempic and Mounjaro are specifically approved by FDA for treating diabetes and not for weight loss, all four are being used by people who want to lose weight. Before you decide whether to take these drugs, here are some things you should know.
What are these drugs and how do they work?
The FDA approved Ozempic in 2017 for the treatment of type 2 diabetes and Wegovy in 2021 for weight loss for adults with obesity or who are overweight and have at least one weight-related health condition. Although these drugs have been on the market for several years, their popularity really exploded in 2023. Mounjaro was approved in the spring of 2022 for Type 2 diabetes and Zepbound was approved in late 2023 for those with obesity or who are overweight with an additional chronic condition such as hypertension. While Ozempic and Mounjaro are not approved specifically for weight loss, doctors may prescribe them anyway – that’s called prescribing it off-label. All four curb hunger and reduce the intake of food. The medications are currently administered by injection once a week, but they may soon be available in pill form.
Both Wegovy and Ozempic are made of semaglutide. Mounjaro and Zepbound are made of tirzepatide. Both mimic the GLP-1 hormone, which is made naturally by the body. GLP-1 does 2 things: 1) It One is to slow the passage of food through the stomach, which helps people feel fuller longer; and 2) it promotes insulin release and helping reduce blood sugar.
What do research studies say?
In August 2023, Wegovy’s maker, Novo Nordisk, claimed in a press release that the drug reduced the risk of serious heart problems. The company described a randomized trial of 17,500 patients with obesity and heart disease, although patients with diabetes were excluded.[2] Half of the participants received regular injections of Wegovy and the other half received a placebo. Rather than publish the results in a peer-reviewed journal, Novo Nordisk publicized their research in a press release that claimed that Wegovy reduced heart attacks, strokes, and deaths by 20% compared to placebo, and this was widely reported in the media. However, this statistic is misleading because it is a relative risk. When the study was finally published in the New England Journal of Medicine on November 11, 2023, the results did not sound as impressive: 8% of the people in the placebo group had had a nonfatal stroke or heart attack or died due to cardiovascular causes, compared to 6.5 percent in the Wegovy group. [3] That decrease from 8% to 6.5% is a 20% decrease, but the difference is only 1.5% for patients considering whether it is a meaningful difference for them.
In August 2023, a study published in the New England Journal of Medicine found that the medication reduced the risk of heart problems for diabetes patients who were at high risk for cardiovascular complications. [4] This study included more than 3,000 patients with type 2 diabetes, who were randomly assigned to receive once-weekly Ozempic or a placebo for 2 years. Results showed that 108 of 1648 patients (6.6%) taking Ozempic either died, had a nonfatal heart attack, or nonfatal stroke, compared to 146 of 1649 patients (8.9%) who took the placebo. This was statistically significant (which means it did not occur by chance), but is a difference of only 2.3%.
Mounjaro has been found to reduce blood pressure, which could improve health, but no published studies have provided evidence that it reduces heart disease.
What are the side effects?
The most common side effects of these GLP-1 medications include stomach issues such as nausea and diarrhea. Some patients experienced persistent vomiting or cyclic vomiting syndrome and severe gastroparesis. Gastroparesis is stomach paralysis and occurs when there is a delay or stopping in food movement from the stomach to the small intestine.
Warnings about other possible serious side effects that are listed on the companies’ websites include inflammation of the pancreas, gallbladder problems, increased risk of low blood sugar, kidney problems, serious allergic reactions, change in vision for people with type 2 diabetes, increased heart rate, and depression and thoughts of suicide.[5]
In January 2024, a new FDA report listed potential links between the medications and extensive hair loss (called alopecia), a swallowing problem that can occur during surgery called aspiration, and thoughts of suicide.[14] A few days later, the FDA announced that their preliminary review did not support an increase in thoughts of suicides among patients taking these drugs, but the FDA also said they had drawn no conclusions based on their preliminary findings and would continue to review new data.
An even more serious side effect is the risk of thyroid cancer. According to a study conducted by the European Medicines Agency (EMA, which is the European version of the FDA), researchers found that using GLP-1 medications for 1-3 years may increase the risk for all types of thyroid cancers.[6]
Concerns about aspiration and suicidal thoughts are not new. For example, in 2023 there were media reports about potential complications from anesthesia for people taking these drugs. The American Society of Anesthesiologists advises that people taking these drugs should make sure to stop taking the medication a week before surgery. People who know they are going to have surgery are advised not to eat for 24 hours before surgery, but since these drugs affect how long food stays in the stomach, a 24-hour fast is not enough to prevent regurgitating food during the operation. This is dangerous because vomiting under anesthesia can cause pneumonia and other fatal problems due to the food and stomach acid getting into the lungs.[7] This risk may be impossible to prevent if someone taking the drug requires emergency surgery.
What Happens if You Lose Weight and Want to Stop Taking the Drug?
Most weight loss strategies work for a limited time; when people stop dieting or exercising, they gain the weight back. Is the same true for the new weight loss drugs such as semaglutide and tirzepatide? Unfortunately, most patients take these drugs for less than 3 months and the number still taking the drug after 1 year is even lower. A study of more than 1,900 patients by researchers at the Cleveland Clinic found that patients’ use of semaglutide and several other weight loss medications dropped from 44% at 3 months to 33% at 6 months and just 19% at 12 months.[8] Regardless of whether they stopped taking the drugs due to side effects, cost, or other reasons, the long-term benefits of these drugs are limited because when they stop taking the drugs, their stomach no longer feels full. A study conducted with almost 2,000 adults without diabetes found that one year after no longer taking Wegovy, participants regained two-thirds of their prior weight loss.[9]
There is still much that is unknown about these drugs. It is unclear how these drugs affect patients after years of use, whether the drugs are effective at maintaining a certain weight after long-term use, and whether most patients will benefit from taking the drugs for a limited period of time or if they need to stay on for the rest of their lives. Current literature suggests that such medications may need to be taken life-long to experience long-term benefits and prevent any negative consequences that come from discontinuing use. [8]
Other Questions to Consider
In 2022, Novo Nordisk spent a total of $11 million to promote their Ozempic and other weight-loss drugs, including $9 million on meals and $2 million on travel for thousands of doctors to promote their weight-loss drugs.[10] That included more than 457,000 meals; nearly 12,000 prescribers had food paid for by the company more than a dozen times in that one year. Buying meals for doctors is not illegal, but this extreme level of “generosity” raises concerns. If these drugs are so effective, why did the company think it necessary to provide all these free meals? And since the drugs became much more popular after the company spent all that money providing free meals to doctors, do you wonder if doctors are prescribing these drugs because they have they been unduly influenced to prescribe them?
Is taking these weight loss drugs right for you?
Ozempic is FDA approved for patients with type 2 diabetes and is not approved for weight loss. Due to the risk of thyroid cancer, if you or any family member has ever had a type of thyroid cancer, taking any of these 4 drugs may be dangerous. Similarly, if you have sensitivity to gastrointestinal problems, these drugs may not be right for you.
In January 2024, Eli Lilly, the maker of Mounjaro and Zepbound, warned against their use for cosmetic reasons. The company reminded physicians and patients that GLP-1 drugs are meant for serious diseases (obesity or Type 2 diabetes) and not for cosmetic weight loss. [15]
Another thing to consider is the cost, which is much higher in the U.S. compared to other countries.[11] If insurance does not cover the cost, one monthly dose of Ozempic costs about $900, and the cost for Wegovy is about $1,350 per month.[12],[13] The cost of Mounjaro is similar to Ozempic and Zepbound costs somewhat less than Wegovy. Since they are relatively new, there are no generic versions. You may be able to lower the costs of these drugs through savings programs or through coverage on your health insurance plan. Many private insurance providers cover these drugs to treat Type 2 diabetes. When used for weight-loss purposes, it is much less likely to be covered. Medicare does not cover these drugs, although patients, doctors, and Congress are pressuring Medicare to do so.
The media attention to these 4 drugs makes it seem that they are the only FDA-approved weight loss drugs. They are not. However, all weight loss drugs have unpleasant and potentially serious side effects, and these 4 seem to be more effective.
If you are eligible and interested in taking these drugs, you should first and foremost make sure to talk to your physician and discuss what to expect, the possible side effects, and your medical history. If you are not eligible for these drugs or are not interested in using them, there are other methods available that can help you lose weight and improve your health if you stick with them. These include exercising daily or regularly, developing healthier eating habits, and knowing when to eat.
[1] Hoffman, S. (2023) The Differences between Saxenda and Wegovy. Very Well Health. https://www.verywellhealth.com/the-differences-between-saxenda-and-wegovy-7564310
[2] Chen, E., and Joseph, A. (2023). Novo’s obesity drug Wegovy lowers cardiovascular risk by 20%, landmark trial finds. STAT+. https://www.statnews.com/2023/08/08/novo-nordisk-wegovy-cardiovascular-risk/
[3] Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., Lingvay, I., Oral, T. K., Michelsen, M. M., Plutzky, J., Tornøe, C. W., & Ryan, D. H. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2307563
[4] Marso, S., Bain, S., Consoli, A., & Eliaschewitz, F. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/nejmoa1607141
[5] Novo Nordisk. (n.d.). Tips for managing common side effects. https://www.wegovy.com/dashboard/my-library/week-02-tips-for-managing-common-side-effects.html#:~:text=thoughts%20of%20suicide.-,The%20most%20common%20side%20effects%20of%20Wegovy%C2%AE%20may%20include,runny%20nose%20or%20sore%20throat.
[6] Bezin, J., Gouverneur, A., Penichon, M., Mathieu, C., Garrel, R., Hillaire-Buys, D., Pariente, A., & Faillie, J.L. (2022). GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. https://diabetesjournals.org/care/article-abstract/46/2/384/147888/GLP-1-Receptor-Agonists-and-the-Risk-of-Thyroid?redirectedFrom=fulltext
[7] Goodman, B. (2023). They took blockbuster drugs for weight loss and diabetes. Now their stomachs are paralyzed. CNN. https://www.cnn.com/2023/07/25/health/weight-loss-diabetes-drugs-gastroparesis/index.html
[8] Most Stop Taking Weight Loss Drugs Within 1 Year. (n.d.). Medscape. Retrieved December 12, 2023, from https://www.medscape.com/viewarticle/most-stop-taking-weight-loss-drugs-within-1-year-2023a1000uiq
[9] Wilding, J. P., Batterham, R. L., Davies, M., Van Gaal, L. F., Kandler, K., Konakli, K., Lingvay, I., McGowan, B. M., Oral, T. K., Rosenstock, J., Wadden, T. A., Wharton, S., Yokote, K., & Kushner, R. F. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism, 24(8), 1553–1564. https://doi.org/10.1111/dom.14725
[10] Florko, N. (2023). Novo Nordisk bought prescribers over 450,000 meals and snacks to promote drugs like Ozempic. STAT+. https://www.statnews.com/2023/07/05/ozempic-rybelsus-novo-nordisk-meals-for-doctors/#:~:text=Novo%20Nordisk%20bought%20prescribers%20over,to%20promote%20drugs%20like%20Ozempic&text=WASHINGTON%20%E2%80%93%20Novo%20Nordisk%20spent,weight%20loss%2Dinducing%20diabetes%20drugs
[11] Amin, K., Telesford. I., Singh, R., & Cox, C. (2023). How do prices of drugs for weight loss in the US compare to peer nations’ prices? Health System Tracker. https://www.healthsystemtracker.org/brief/prices-of-drugs-for-weight-loss-in-the-us-and-peer-nations/?utm_campaign=morning_rounds&utm_medium=email&_hsmi=270760455&_hsenc=p2ANqtz-_P2SZN9DLjS_l7fSn8hrgS8xRf4YvJIonV0X-iRtKF3FtcWbgsMJd-K6tDV2u12XNFMEesDCulwlbdwkw74D1S-2WqXQ&utm_content=270760453&utm_source=hs_email#List%20prices%20of%20drugs%20used%20for%20weight%20loss%20in%20the%20U.S.%20and%20peer%20nations
[12] Wilson, A. (2023). How much does Ozempic cost without insurance?. RO. https://ro.co/weight-loss/ozempic-cost-without-insurance/
[13] Wilson, A. (2023). How much does Wegovy cost? RO. https://ro.co/weight-loss/wegovy-cost/
[14] FDA Looking Into New Risks With Popular Weight-Loss Drugs. (n.d.). Retrieved January 9, 2024, from https://www.usnews.com/news/health-news/articles/2024-01-04/fda-looking-into-new-risks-with-popular-weight-loss-drugs
[15] Open Letter Regarding the Use of Mounjaro® (tirzepatide) and ZepboundTM (tirzepatide) | Eli Lilly and Company. (n.d.). Retrieved January 12, 2024, from https://investor.lilly.com/news-releases/news-release-details/open-letter-regarding-use-mounjaror-tirzepatide-and-zepboundtm