Mounjaro leads to significantly more weight loss than Ozempic, study suggests

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By Deidre McPhillips, CNN

(CNN) — People taking tirzepatide injections lost more weight and were more likely to reach specific weight loss targets than those taking semaglutide, according to a new study.

Researchers from Truveta, a health data analytics company, analyzed electronic health records for more than 18,000 adults, all of whom had overweight or obesity, who were using these medications in the real world between May 2022 and September 2023. The findings were published Monday in the JAMA Internal Medicine medical journal.

Both medications were effective: The vast majority of people using either tirzepatide or semaglutide lost at least 5% of their starting body weight after one year of use. But 82% of people taking tirzepatide reached this important clinical benchmark, compared with about 67% of those taking semaglutide. And people taking tirzepatide were more than twice as likely to lose at least 15% of their starting weight than those taking semaglutide: about 42% compared with 18% after one year of use.

Average weight loss was also consistently higher among those taking tirzepatide over time. After three months, people taking tirzepatide had lost about 6% of their body weight, on average, compared with an average of less than 4% loss among those taking semaglutide. At six months, average weight loss was 10% on tirzepatide and about 6% on semaglutide. And by one year, average weight loss was nearly double for those taking tirzepatide: more than 15%, compared with about 8% for those taking semaglutide.

Tirzepatide and semaglutide both 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.

The US Food and Drug Administration has approved versions of tirzepatide and semaglutide to treat both type 2 diabetes and obesity. Eli Lilly manufactures tirzepatide under the brand name Mounjaro for diabetes and Zepbound for chronic weight management, while Novo Nordisk manufacturers semaglutide as Ozempic for diabetes and Wegovy for weight management.

The FDA approved higher doses of both tirzepatide and semaglutide to treat weight loss, but the new study looked only at the doses to treat type 2 diabetes.

About half of the people who were included in this study had type 2 diabetes, while the other half had no indication of a diabetes diagnosis in their health records and were probably using these medications off-label for weight management at their doctor’s discretion.

When the findings from this study were first released in a preprint last year, Novo Nordisk told CNN that it wasn’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.

According to the new study, individuals with type 2 diabetes had less significant weight loss than those without a diagnosis — but average weight loss was still greater among those taking tirzepatide.

The researchers did not track mild gastrointestinal side effects such as nausea and vomiting, noting that these types of complaints might not be captured in patient records consistently. But the risk of more serious adverse outcomes — such as bowel obstruction, gasteoparesis or pancreatitis — were found to be similar among those taking tirzepatide and semaglutide.

Along with side effects, people who did not lose weight while taking these medications may be more likely to stop or switch drugs, the researchers say. Discontinuation was common — more than half of patients stopped their treatment before the end of the study — but rates were similar among those taking tirzepatide and those taking semaglutide.

The findings from this study align with clinical trial results, but the study authors note that more research is needed to compare the effects that tirzepatide and semaglutide have on other key health outcomes, such as heart-related events.

CNN’s Brenda Goodman contributed to this report.

Correction: This story has been corrected to more accurately reflect the main outcomes measured in the study.

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