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In the first large-scale head-to-head study, people taking Eli Lilly's diabetes drug Munjaro lost significantly more weight than those taking Novo Nordisk's Ozempic, but side effects, withdrawal rates, and effects on diabetes were similar.
Both drugs are in the same class of medications, known as GLP-1, but Lilly's drug, tirzepatide, sold under the brands Mounjaro for diabetes and Zepbound for weight-loss, contains a second effect that appears to enhance its effectiveness. Separate studies have suggested that tirzepatide may be more effective at helping people lose weight than semaglutide, sold by Novo Nordisk under the brand name Ozempic for diabetes and at higher doses as a weight-loss drug sold under the brand name Wegovy.
In the new study, The study was published Monday in the journal JAMA Internal Medicine.compared data from more than 18,000 patients who started taking either of the two drugs between May 2022 and September 2023. The study relied on electronic medical records from Truveta, a collection of health systems across the country that has access to data on more than 100 million patients.
At the time, tirzepatide had not yet been approved as a weight loss drug, only as a diabetes treatment, so the study did not include all people with type 2 diabetes, but only looked at people who had a prescription for two type 2 diabetes medications.
By November last year, more than half of people taking either drug had stopped taking it (56% of those taking tirzepatide and 53% of those taking semaglutide). Although the survey did not identify reasons why, many reported side effects from the drugs, mostly gastrointestinal symptoms such as vomiting and nausea.
The study did not report whether people who stopped the diet regained the weight they had lost. Research has shown that so-called yo-yo dieting can lead to more health problems than just weight gain.
However, GLP-1 is by far one of the most effective and safest weight loss drugs ever developed.More than 70% of Americans meet the medical definition of overweight, and 40% meet the definition of obese.
“We've been tracking the use of GLP-1 for the past few years and have seen a dramatic increase in its use,” said study leader Tricia Rodriguez of Truveta Research, who said the drugs are “really revolutionizing the treatment of diabetes and obesity.”
A clear winner? Not so soon, says Novo
Novo Nordisk disputed the study's conclusions.
“The ideal way to compare the two treatments would be an adequately powered head-to-head randomized clinical trial (RCT) in obesity. Currently, no head-to-head trials comparing tirzepatide with semaglutide 2.4 mg have been completed,” the company said in a statement sent by Allison Schneider, the company's director of media relations and issues management.
The 2.4 mg dose is the highest dose of semaglutide commonly used for weight loss. The highest doses used to treat diabetes are lower, meaning the dose used in this study in people with diagnosed diabetes was below the optimal dose for weight loss.
For tirzepatide, the maximum dosage is the same whether it is taken for weight loss or for diabetes.
Specific lessons learned from the study
The study found that people taking tirzepatide were almost twice as likely to lose 5% of their body weight, 2.5 times as likely to lose 10% of their body weight, and more than three times as likely to lose 15% of their body weight compared to people taking semaglutide.
After three months of taking each drug, patients taking tirzepatide lost an average of about 6% weight, while those taking semaglutide lost just under 4%. After six months, patients taking tirzepatide lost 10% weight, while those taking semaglutide lost 6%. And after a year, patients taking tirzepatide lost 15% weight, while those taking semaglutide lost 8%.
As other studies have found, people with diabetes lost less weight with the drug than obese people without diabetes.
Of the 18,386 people studied, 70% were women, 77% were white, and 11% were black, and just over half had type 2 diabetes. Their average BMI was 39 and their average age was 52. More than one in five had been diagnosed with depression.
Obesity, diabetes and depression often overlap because they're all so common, medications for mental illnesses are linked to weight gain and the development of diabetes, and they affect each other, said Dr. Katherine Sanders, an obesity medicine expert at Weill Cornell Medicine in New York.
“Obesity and diabetes can make depression worse, and depression can make obesity and diabetes worse,” she said.
Why do they drop out?
Doctors who prescribe these highly effective drugs say side effects and limited availability cause many patients to stop taking them.
Experts say side effects can usually be controlled with proper medical monitoring and appropriate increases in dosage.
“Patients need more than just a prescription for a GLP-1 drug in the last few minutes of a busy appointment,” said Sanders, who is also co-founder of obesity treatment provider IntelliHealth.
Getting people to take these medications and stick with them requires individualized care, time and “a huge amount of education and support,” she said.
Both drugs are meant to be taken in a stepwise manner, starting with a low dose and then gradually increasing it. If patients can't tolerate the increased dose, they're usually continued on the lower dose indefinitely or until side effects subside, said Dr. Fatima Cody Stanford, an obesity medicine specialist at Massachusetts General Hospital in Boston.
According to Dr. Cody Stanford, the only patients who stop taking GLP-1 for medical reasons are about one in 1,000 who develop pancreatitis, a painful inflammation of the pancreas, and about 15% who don't experience significant weight loss even after taking the drug for a long time.
Cody Stanford said he often has to convince those people that drugs others call “miracle” don't work for them.
“This isn't a 'try harder' situation,” she said. “If it works, it works.”
Cost and access issues
A more common reason for discontinuing GLP-1 use is lack of reliable, consistent supply, according to Cody Stanford.
Both drugs have been difficult to obtain due to supply constraints..
Novo Nordisk says it has provided Wegoby to more than one million Americans since 2021, and the highest doses, 1.7mg and 2.4mg, are now fully available, “which is consistent with our goal of doing our best to ensure continuity of care for existing patients as doses increase in accordance with labeling,” the company said in a statement.
“At this time, we cannot speculate on when Wegovy will be fully available in all doses, but we are working hard to increase manufacturing capacity and supply to meet patient needs,” the statement said.
For the latest supply information, please see below. Wigovi Supply.
Lilly declined to comment because it was not involved in the new study, but it has struggled to meet demand for tirzepatide, especially since it was approved as a weight-loss drug under the brand name Zepbound.
Fatima Cody Stanford said Novo's semaglutide was now available for her patients, but Lilly's tirzepatide was no longer.
Both drugs cost about $1,000 a month at the maximum dose, but Novo Nordisk's weight-loss semaglutide formulation, Wegovy, is more expensive than its diabetes drug Ozempic because of its higher maximum dose.
Cody Stanford said high prices and access issues are making it hardest for those who need the medicines the most to get them.
Most of the study participants were middle-class, white women, and patients prescribed tirzepatide were even more likely to be white and female, Dr. Rodriguez said. There are differences between patients taking tirzepatide and those taking semaglutide, and some patients can't take either, Dr. Rodriguez said.
Black, Hispanic and Native American women have the highest rates of obesity and diabetes, yet typically lack insurance coverage for GLP-1. “There's a disparity between who has and doesn't have insurance coverage for these new therapies,” Cody-Stanford said.
