Both Ozempic, or semaglutide, and Mounjaro, or tirzepatide, mimic the effects of the gut hormone GLP-1, which stimulates the body's production of insulin and slows the passage of food through the stomach. GLP-1 also signals the brain to help control appetite. Tirzepatide also stimulates a second gut hormone, called GIP, which may help boost its effects.
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The drugs are prescribed to treat type 2 diabetes but have gained new popularity because they may also help people lose substantial amounts of weight.
The new study is a preprint that has not been peer-reviewed or published in a professional journal. Its results are in line with observations from clinical trials, and many doctors had suspected that tirzepatide might be more potent after seeing the results in their diabetes patients. But so far, there haven't been many studies that have compared the drugs head-to-head, especially in people who don't have diabetes. One such investigation is underway, but results aren't expected for more than a year.
"Over 70% of American adults have overweight or obesity, and so there's this huge potential for these medications to be used and [there's] really a lack of information," said lead study author Dr. Patricia Rodriguez, a senior applied scientist at Truveta Research.
The study wasn't sponsored by either of the drugs' manufacturers. Instead, it was initiated by Truveta, a data analytics company owned and operated by 30 US health care systems. Truveta combines anonymous patient records from these hospitals and uses them to answer research questions.
Comparing weight loss medications
Because of their weight-loss benefits, the US Food and Drug Administration has approved higher doses of both tirzepatide and semaglutide for weight loss under the names Zepbound and Wegovy, respectively. The new study looked only at the doses approved to treat type 2 diabetes, which may limit its conclusions. The records spanned the period between May 2022 and September 2023.
Rodriguez and her team combed through thousands of patient records to find overweight and obese adults on Mounjaro or Ozempic.
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Of the more than 18,000 people included in the study, just over half - 52% - had type 2 diabetes. The other 48% had no history of diabetes documented in their medical records, so researchers reasoned that this group of more than 9,000 people was probably taking the medications off-label at their doctor's discretion, solely for weight loss.
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People lost more weight the longer they stayed on the medication, but many did not continue taking these drugs. Roughly half of people included in the study discontinued them during the study period.
The authors note that it's hard to say why people stopped filling their prescriptions. Both medications in the study were in shortage, and so they may have been difficult to find.
The most common side effects noted in the medical records were nausea and vomiting, which were reported for about 1 in 5 people on the medications. Gallstones were reported for roughly 1 in 6. The study authors note that side effects were very similar between the medications, and they found no significant differences in the rates of any adverse event
People lost more weight on the medications if they didn't have diabetes, but even if they did, those taking Mounjaro lost a greater percentage of their starting weight than those taking Ozempic.
At three months, the average weight loss was about 6% for Mounjaro users, compared with nearly 4% for those on Ozempic. After six months, the average weight loss on Mounjaro was 10%, compared with 6% on Ozempic. At 12 months, people had dropped an average 15% of their body weight on Mounjaro, compared with about 8% on Ozempic. After the researchers adjusted their data for potential sources of bias, those differences narrowed.
The best one is the one that works
The study's results aren't a big departure from results posted in clinical trials, so they aren't terribly surprising, says Dr. Mopelola Adeyemo, who treats people with diabetes and obesity at the University of California at Los Angeles.
Adeyemo says that ultimately, the best weight loss drug for an individual is going to be the one that works for them. She has patients who can't tolerate one form of a GLP-1 medication like Ozempic or Mounjaro but can take a different one.
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"I think there's going to be roles for both of them, definitely, because both have been shown to not only help with weight loss but also diabetes and another cardiovascular benefits, as well," Adeyemo said.
Novo Nordisk, the company that makes Ozempic for diabetes and Wegovy for weight loss, said the study isn't a fair comparison.
"The doses of semaglutide evaluated in this analysis have not been investigated for chronic weight management, and there are no head-to-head trials that have reported which evaluate Wegovy and tirzepatide." a spokesperson said in a statement.
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The company notes that semaglutide is taken at a higher dose when used for weight loss.
"We agree completely," Rodriguez said. "We expect that in the obesity labeled medications, we would expect that people would lose more weight because the dosages are quite higher."
Eli Lilly, the company that makes Mounjaro and Zepbound, said it doesn't condone the off-label use of its medication. It's urging patience while it works to get more information.
"Our SURMOUNT-5 trial, which is a head-to-head trial comparing tirzepatide (Zepbound) and semaglutide (Wegovy) for the treatment of obesity or overweight with weight-related comorbidities, is expected to read out in 2025," a spokesperson said in an email.
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