Weight-loss medications continue to grow in popularity as an anti-obesity tool — but are some more effective than others?

The question was explored in a new study published this month in The New England Journal of Medicine.

Researchers compared the safety and efficacy of tirzepatide (brand name Zepbound) and semaglutide (brand name Wegovy) in a 72-week clinical trial.

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The randomized, controlled trial — called SURMOUNT-5 — included 751 people throughout the U.S. and Puerto Rico who had obesity but not type 2 diabetes.

“Doctors, insurance companies and patients are always asking, ‘Which drug is more effective?’” said Dr. Louis Aronne, director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, in the release. “This study allowed us to do a direct comparison.” 

“The results are consistent with — in fact, almost identical to — what we’ve seen in trials in which these drugs were evaluated independently,” added Aronne, who was a principal investigator in the trial.

The study found that tirzepatide achieved greater weight loss, with participants shedding about 50 pounds (20.2% of their body weight).

“Doctors, insurance companies and patients are always asking, ‘Which drug is more effective?’”

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The group taking semaglutide lost an average of 33 pounds or 13.7% of their baseline weight, according to a press release summarizing the study outcome.

Overall, 32% of the people taking tirzepatide lost at least 25% of their body weight; semaglutide users lost around 16%.

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Tirzepatide users also reported a “greater reduction in waist circumference” than those on semaglutide.

The likely reason for tirzepatide’s greater effectiveness is that it uses a “dual mechanism of action,” according to Aronne.

“Whereas semaglutide works by activating receptors for a hormone called glucagon-like peptide 1, or GLP-1, tirzepatide mimics not only GLP-1, but also an additional hormone, glucose-dependent insulinotropic peptide (GIP),” the release stated.

“Together, these actions reduce hunger, lower blood-glucose levels and affect fat cell metabolism.”

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Additional trials are actively exploring whether tirzepatide also reduces the risk of heart attack and stroke, a benefit that has been linked to semaglutide.

The study was led by an investigator at Weill Cornell Medicine and NewYork-Presbyterian. It was also conducted with the University of Texas McGovern Medical School, the David Geffen School of Medicine at the University of California, Los Angeles, the University College Dublin and Eli Lilly (maker of Zepbound).

The participants all received guidance regarding nutrition and exercise.

The reported side effects were very similar for the two drugs, with 44% of people experiencing nausea and 25% having abdominal pain.

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Dr. Ada Londono, M.D., a board-certified obesity and internal medicine primary care physician with PlushCare — a virtual health platform offering primary care, therapy and weight management services — said she was not surprised by the study’s findings.

“The results are consistent with prior trials, confirming tirzepatide’s advantage over semaglutide’s single GLP-1 action,” Londono, who is based in New York City, told Fox News Digital.

Beyond weight loss, semaglutide has also shown potential benefits for cardiovascular health, sleep apnea and kidney disease, she noted. 

“These findings highlight the need for continued research to understand tirzepatide’s broader health impacts,” she said. “It’s encouraging to see ongoing studies exploring the full potential of GLP-1 medications beyond weight management.”

Londono said these treatments can come with side effects. 

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“Most people on these medications only report mild symptoms, but some have experienced more serious reactions, such as pancreatitis,” she told Fox News Digital. 

“This underscores the importance of reviewing your medical history and discussing any concerns with your healthcare provider.”

Potential limitations

The study did have some limitations — chiefly that it was not a blinded analysis and participants knew which medication they were receiving. This could introduce some level of bias, the researchers acknowledged.

Londono pointed out that while the study’s findings are “promising,” it was funded by Eli Lilly, the manufacturer of Zepbound.

“This may raise questions about potential conflicts of interest,” she said. “Additionally, the open-label design and 72-week duration may limit objectivity and long-term insight.”

While the study primarily looked at the impact of the medications, experts agreed there are other factors that play a role in successful weight management.

“Weight loss is biological, but it’s also emotional, and whole-person support can make the difference between short-term results and sustainable health,” Dr. Rekha Kumar, chief medical officer at the weight care program Found and a practicing endocrinologist in New York City, told Fox News Digital.

Kumar emphasized the importance of working with a physician to choose a weight-loss medication that matches the patient’s personal goals and health status.

“Both Wegovy and Zepbound have demonstrated clinically significant weight reduction.”

“For example, if a patient has fatty liver, we will choose the GLP-1 that is proven to work best for liver disease,” she said. 

Looking ahead, the researchers plan to investigate new versions of weight-loss drugs, including retatrutide, which mimics the hormones GLP-1, GIP and glucagon, according to the release.

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“Even though drugs like tirzepatide and semaglutide work really well, better than anything we have ever seen, we still have people who don’t respond to them,” said Aronne. 

“So, moving forward, we want to keep trying to do better.”

A spokesperson from Novo Nordisk, the company that makes Wegovy (semaglutide), sent a statement to Fox News Digital.

“Across the respective clinical trial programs and in SURMOUNT-5, both Wegovy and Zepbound have demonstrated clinically significant weight reduction,” the company said. “It is important to recognize that the comprehensive management of obesity goes beyond weight reduction alone.”

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The spokesperson also pointed out that in a previous trial, adults who were obese or overweight and who took Wegovy along with diet and exercise lost an average of 15.2% of their weight (~35 pounds) at the two-year mark, compared with 2.6% (~6 pounds) for patients taking a placebo.