Zepbound beats Wegovy for weight loss in first head-to-head trial of GLP-1 drugs

The first study to put two GLP-1 weight loss drugs head-to-head found Zepbound helped people lose more weight than Wegovy. — Image credit: AP Photo/JoNel Aleccia

Summary

Zepbound vs. Wegovy

The first study to put two GLP-1 weight loss drugs head-to-head found Zepbound helped people lose more weight than Wegovy.

Weight loss

Zepbound users lost 20% of their body weight on average compared to Wegovy users. Who lost 14% on average.

Numbers game

The study’s author says both drugs are important tools for treating obesity, which impacts 40% of American adults, according to the CDC.

Full story

As weight loss injections continue to gain more popularity, researchers are getting more opportunities to study their effects. Now, the first head-to-head study between two of the most well-known medications is providing some insight on the question: Which one is best?

What are the details of the study?

Researchers studied results for those taking Zepbound and Wegovy. They found Zepound users lost nearly 50% more weight than Wegovy users.

The study, which was funded by Zepbound maker Eli Lilly, was conducted by the Comprehensive Weight Control Center at Weill Cornell Medicine and published in The New England Journal of Medicine on Sunday, May 11.

The trial included 751 people from across the U.S. who were overweight or had obesity and at least one other weight-related health problem, but not diabetes.

Zepbound vs. Wegovy

Though similar, Zepbound and Wegovy have different active ingredients. Zepbound is tirzepatide-based, while Wegovy uses semaglutide.

Unbiased. Straight Facts.^TM

More than 40% of U.S. adults have obesity, with that number tripling since 1975.

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Both drugs work similarly, mimicking hormones in the gut and brain that regulate appetite and feelings of fullness. However, while both drugs target the hormone known as GLP-1, tirzepatide also targets a second hormone called GIP.

GLP-1 stimulates insulin secretion and suppresses glucagon, while also impacting appetite and slowing gastric emptying. GIP also stimulates insulin, but can enhance glucagon secretion and impact how the body stores fat.

What were the results?

By the end of the trial, researchers say those who took Zepbound lost about 20% of their body weight on average, while Wegovy users lost nearly 14% of theirs.

More than three-quarters of patients in the study reported at least one side effect, mostly mild to moderate gastrointestinal issues. About 6% of those taking tirzepatide left the trial because of the side effects, compared to 8% of those taking semaglutide.

What’s the bottom line?

Dr. Louis Aronne, who led the study, said that while it may appear one drug is more effective than the other, both are important tools for treating obesity, a disease that affects about 40% of American adults.

“The point of these medications is to improve health,” Dr. Aronna said as he presented the findings Sunday at the European Congress on Obesity in Spain. “The majority of people won’t need the most effective medication.”

At least 1 in 8 U.S. adults have reported using some type of GLP-1 drug, according to a 2024 survey by KFF.

Kaleb Gillespie (Video Editor), Mohammed Ali (Senior Motion Designer), and Devin Pavlou (Digital Producer) contributed to this report.

Tags: CDC, Centers for Disease Control and Prevention, Eli Lilly, GLP-1, Health, Medication, Novo Nordisk, Obesity, prescription drugs, Study, Weight Loss

[Craig Nigrelli]

WEIGHT LOSS INJECTIONS HAVE GAINED MORE AND MORE POPULARITY IN RECENT YEARS – AND AS MORE PEOPLE USE THEM, RESEARCHERS ARE GETTING MORE OPPORTUNITIES TO STUDY THEIR EFFECTS.

WITH MULTIPLE SHOTS OUT THERE TO CHOOSE FROM – THE QUESTION HAS LONG BEEN WHICH ONE WORKS BEST?

NOW, THE FIRST HEAD-TO-HEAD STUDY OF TWO DIFFERENT MEDICATIONS IS GIVING US SOME INSIGHT.

RESEARCHERS STUDIED RESULTS FOR THOSE TAKING TIRZEPATIDE (terr-zep-uh-tide), THE ACTIVE INGREDIENT IN ZEPBOUND AND THOSE TAKING SEMAGLUTIDE (sim-uh-glue-tide), THE INGREDIENT IN WEGOVY – AND FOUND ZEPOUND USERS LOST NEARLY 50 PERCENT MORE WEIGHT THAN WEGOVY USERS.

EVEN THOUGH THEY’RE DIFFERENT, BOTH DRUGS WORK IN BASICALLY THE SAME WAY: MIMICKING HORMONES IN THE GUT AND BRAIN THAT REGULATE APPETITE AND FEELINGS OF FULLNESS.

BUT WHILE BOTH DRUGS TARGET THE HORMONE KNOWN AS G-L-P-1 – TIRZEPATIDE **ALSO** TARGETS A SECOND HORMONE, CALLED G-I-P.

GLP-1 IMPACTS THE APPETITE AND SLOWS GASTRIC EMPTYING, WHILE GIP IMPACTS HOW THE BODY STORES FAT

BY THE END OF THE TRIAL – RESEARCHERS SAY THOSE WHO TOOK ZEPBOUND LOST ABOUT 20 PERCENT OF THEIR BODY WEIGHT ON AVERAGE… WHILE WEGOVY USERS LOST NEARLY 14 PERCENT OF THEIRS.

IT’S IMPORTANT TO NOTE THIS STUDY WAS FUNDED BY ELI LILLY – THE MAKER OF ZEPBOUND.

WEGOVY IS MADE BY NOVO NORDISK.

THE DOCTOR WHO LED THE STUDY SAID WHILE IT MAY APPEAR ONE DRUG IS MORE EFFECTIVE THAN THE OTHER… BOTH ARE IMPORTANT TOOLS FOR TREATING OBESITY, A DISEASE AFFECTING ABOUT 40 PERCENT OF AMERICAN ADULTS.

ACCORDING TO A 20-24 SURVEY BY K-F-F… AT LEAST 1 IN 8 U-S ADULTS REPORTED USING SOME TYPE OF G-L-P-1 DRUG,.

TO STAY UP TO DATE ON ALL YOUR LATEST HEALTH HEADLINES LIKE THIS – MAKE SURE YOU DOWNLOAD THE STRAIGHT ARROW NEWS APP TODAY.

Why this story matters

A new clinical trial comparing Zepbound (tirzepatide) and Wegovy (semaglutide) provides evidence on the effectiveness and side effects of leading obesity medications, informing treatment options for the portion of the population affected by obesity.

Treatment efficacy

The study, commissioned by Zepbound's manufacturer, found that patients using it lost a higher percentage of body weight than those using Wegovy, offering new data on how different medications may benefit individuals with obesity.

Side effects and safety

More than three-quarters of all trial participants reported mild to moderate gastrointestinal side effects, highlighting the need to weigh efficacy against potential adverse events when considering obesity treatments.

Access and public health impact

The high prevalence of obesity and growing use of weight-loss drugs raises questions about access, cost, and overall health care strategies in managing this widespread chronic disease.

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Synthesized coverage insights across 113 media outlets

Behind the numbers

The comparison trial evaluated 751 adults with obesity or overweight (no diabetes) over 72 weeks. According to published data, participants taking Zepbound (tirzepatide) lost an average of 20.2% of their body weight (roughly 50 pounds), while those on Wegovy (semaglutide) lost 13.7% (about 33 pounds). Both saw health improvements, but also reported gastrointestinal side effects.

Global impact

Demand for effective obesity medications extends globally, with rising sales of both Zepbound and Wegovy. The trend influences health care approaches to obesity in multiple countries and spurs new regulatory approvals, reimbursement negotiations, and discussions about long-term impacts on public health planning and healthcare budgets worldwide.

History lesson

Previous generations of weight-loss drugs often produced modest results and raised safety concerns, leading to withdrawals. Recent advances with GLP-1/GIP agonists, supported by large clinical trials, have led to improved outcomes and safety profiles. The head-to-head study presented here is the first direct comparison of these two major drugs within this newer class.

Sources

Bias comparison

Media outlets on the left frame the Zepbound vs. Wegovy trial with a cautious yet commercially aware lens, emphasizing "blockbuster drugs" and highlighting affordability and access barriers, thereby blending clinical efficacy with socio-economic concerns.
Not enough coverage from media outlets in the center to provide a bias comparison.
Media outlets on the right foreground Zepbound’s quantifiable superiority—“50% more weight loss” and labels like the “King Kong” jab—using emphatic, competitive language that celebrates clear winners and market implications, especially around CVS’s formulary exclusion of Zepbound.

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Media landscape

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113 total sources

Key points from the Left

Participants taking Eli Lilly's obesity drug, Zepbound, lost nearly 50% more weight than those using Novo Nordisk's Wegovy, with an average loss of 50 pounds over 72 weeks compared to 33 pounds.
The trial included 751 adults with obesity and showed that 32% lost a quarter of their body weight with Zepbound versus 16% with Wegovy.
Dr. Louis Aronne noted that both Zepbound and Wegovy are important tools for treating obesity, which affects about 40% of American adults.
Dr. Angela Fitch emphasized the need for a range of medications to address the widespread obesity issue in the U.S.

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Key points from the Center

Eli Lilly announced on May 11, that Zepbound led to greater weight loss than Wegovy in the SURMOUNT-5 trial involving 751 overweight or obese adults across the U.S. and Puerto Rico.
The trial involved adults without diabetes who were either obese or overweight and had one or more associated health conditions related to their weight, aiming to show that Zepbound is more effective than Wegovy in reducing body weight after 72 weeks.
Participants taking Zepbound lost an average of 20.2% of body weight , outperforming Wegovy users who lost 13.7% , with Zepbound also reducing waist circumference more than Wegovy.
Leonard Glass of Lilly highlighted that Zepbound achieved notably greater weight loss than Wegovy in the SURMOUNT-5 trial, while Louis Aronne emphasized that these findings reinforce tirzepatide’s role as an effective therapy for obesity.
The findings imply Zepbound offers a potent option for obesity management amid rising GLP-1 drug use, though side effects were mostly mild-to-moderate and access and affordability remain challenges.

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See Hide headlines from Center sources 38 sources

Key points from the Right

People taking Zepbound lost nearly 50% more weight than those taking Wegovy, according to a study in the New England Journal of Medicine.
Participants taking Zepbound lost an average of 50 pounds over 72 weeks, while those on Wegovy lost 33 pounds.
Both drugs improved health markers, and over 75% of patients reported mild to moderate side effects, mostly gastrointestinal problems.

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