People taking Eli Lilly's obesity drug, Zepbound, lost nearly 50% more weight than those using rival Novo Nordisk's Wegovy in the first head-to-head study of the blockbuster medications.
Clinical trial participants who took tirzepatide, the drug sold as Zepbound, lost an average of 50 pounds (22.8 kilograms) over 72 weeks, while those who took semaglutide, or Wegovy, lost about 33 pounds (15 kilograms). That's according to the study funded by Lilly, which was published Sunday in the New England Journal of Medicine.
Both drugs are part of a new class of medications that work by mimicking hormones in the gut and brain that regulate appetite and feelings of fullness. But tirzepatide targets two such hormones, known as GLP-1 and GIP, while semaglutide targets GLP-1 alone, said Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine.
“Two drugs together can produce better weight loss,” said Aronne, who led the study and presented the findings Sunday at the European Congress on Obesity in Spain.
While tirzepatide won out in what Aronne said many view as “a drag race of efficacy,” both are important tools for treating obesity, which affects about 40% of American adults.
“The point of these medications is to improve health,” he said. “The majority of people won't need the most effective medication.”
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. Participants received weekly injections of the highest tolerated doses of Zepbound, either 10 milligrams or 15 milligrams, or Wegovy, 1.7 milligrams or 2.4 milligrams.
By the end of the trial, those who took Zepbound lost about 20% of their body weight on average, compared with a nearly 14% loss for those who took Wegovy. The tirzepatide group trimmed about 7 inches (17.8 centimeters) from their waist circumference, compared to about 5 inches (12.7 centimeters) with semaglutide. In addition, nearly 32% of people taking Zepbound lost at least a quarter of their body weight, compared to about 16% of those taking Wegovy, the study found.
Weight loss was about 6% lower in men than in women in both groups, the authors noted. As participants in both groups lost more weight, they saw improvements in health markers such as blood pressure, blood fat and blood sugar levels.
More than three-quarters of patients taking both drugs reported at least one side effect, mostly mild to moderate gastrointestinal issues such as nausea, constipation, diarrhea and vomiting. About 6% of participants taking Zepbound left the trial because of adverse events, compared with 8% of those taking semaglutide.
The GLP-1 drugs have become increasingly popular, with at least 1 in 8 U.S. adults reporting their use, according to a 2024 survey by KFF, a independent health policy research organization. Zepbound generated $4.9 billion in global sales last year. Wegovy brought in nearly $8.8 billion (58.2 billlion Danish kroner).
Access and affordability have limited wider use of the drugs. Tirzepatide and semaglutide were removed recently from a list of drug shortages by the U.S. Food and Drug Administration. Both manufacturers recently released programs that cut costs to about $500 per month or less, depending on the dose.
Other factors can affect access. This week, CVS Health said Wegovy will become the preferred option on its standard formulary, or list of covered drugs, as of July 1. Zepbound will be excluded.
It's important to have a range of drugs to treat a disease as widespread as obesity in the U.S., said Dr. Angela Fitch, chief medical officer of knownwell, an obesity care company. Wegovy has been found to cut the risk of serious heart problems by 20%, she noted. A drug may work well for one patient, but not for others.
“We're going to need to use them all just because we have so many patients who need treatment,” she added.
AP Health Writer Tom Murphy in Indianapolis contributed to this report.
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.
Boxes for the medications Wegovy and Zepbound are arranged for a photograph in California on Thursday, May 8, 2025. (AP Photo/JoNel Aleccia)
WASHINGTON (AP) — Becky Pepper-Jackson finished third in the discus throw in West Virginia last year though she was in just her first year of high school. Now a 15-year-old sophomore, Pepper-Jackson is aware that her upcoming season could be her last.
West Virginia has banned transgender girls like Pepper-Jackson from competing in girls and women's sports, and is among the more than two dozen states with similar laws. Though the West Virginia law has been blocked by lower courts, the outcome could be different at the conservative-dominated Supreme Court, which has allowed multiple restrictions on transgender people to be enforced in the past year.
The justices are hearing arguments Tuesday in two cases over whether the sports bans violate the Constitution or the landmark federal law known as Title IX that prohibits sex discrimination in education. The second case comes from Idaho, where college student Lindsay Hecox challenged that state's law.
Decisions are expected by early summer.
President Donald Trump's Republican administration has targeted transgender Americans from the first day of his second term, including ousting transgender people from the military and declaring that gender is immutable and determined at birth.
Pepper-Jackson has become the face of the nationwide battle over the participation of transgender girls in athletics that has played out at both the state and federal levels as Republicans have leveraged the issue as a fight for athletic fairness for women and girls.
“I think it’s something that needs to be done,” Pepper-Jackson said in an interview with The Associated Press that was conducted over Zoom. “It’s something I’m here to do because ... this is important to me. I know it’s important to other people. So, like, I’m here for it.”
She sat alongside her mother, Heather Jackson, on a sofa in their home just outside Bridgeport, a rural West Virginia community about 40 miles southwest of Morgantown, to talk about a legal fight that began when she was a middle schooler who finished near the back of the pack in cross-country races.
Pepper-Jackson has grown into a competitive discus and shot put thrower. In addition to the bronze medal in the discus, she finished eighth among shot putters.
She attributes her success to hard work, practicing at school and in her backyard, and lifting weights. Pepper-Jackson has been taking puberty-blocking medication and has publicly identified as a girl since she was in the third grade, though the Supreme Court's decision in June upholding state bans on gender-affirming medical treatment for minors has forced her to go out of state for care.
Her very improvement as an athlete has been cited as a reason she should not be allowed to compete against girls.
“There are immutable physical and biological characteristic differences between men and women that make men bigger, stronger, and faster than women. And if we allow biological males to play sports against biological females, those differences will erode the ability and the places for women in these sports which we have fought so hard for over the last 50 years,” West Virginia's attorney general, JB McCuskey, said in an AP interview. McCuskey said he is not aware of any other transgender athlete in the state who has competed or is trying to compete in girls or women’s sports.
Despite the small numbers of transgender athletes, the issue has taken on outsize importance. The NCAA and the U.S. Olympic and Paralympic Committees banned transgender women from women's sports after Trump signed an executive order aimed at barring their participation.
The public generally is supportive of the limits. An Associated Press-NORC Center for Public Affairs Research poll conducted in October 2025 found that about 6 in 10 U.S. adults “strongly” or “somewhat” favored requiring transgender children and teenagers to only compete on sports teams that match the sex they were assigned at birth, not the gender they identify with, while about 2 in 10 were “strongly” or “somewhat” opposed and about one-quarter did not have an opinion.
About 2.1 million adults, or 0.8%, and 724,000 people age 13 to 17, or 3.3%, identify as transgender in the U.S., according to the Williams Institute at the UCLA School of Law.
Those allied with the administration on the issue paint it in broader terms than just sports, pointing to state laws, Trump administration policies and court rulings against transgender people.
"I think there are cultural, political, legal headwinds all supporting this notion that it’s just a lie that a man can be a woman," said John Bursch, a lawyer with the conservative Christian law firm Alliance Defending Freedom that has led the legal campaign against transgender people. “And if we want a society that respects women and girls, then we need to come to terms with that truth. And the sooner that we do that, the better it will be for women everywhere, whether that be in high school sports teams, high school locker rooms and showers, abused women’s shelters, women’s prisons.”
But Heather Jackson offered different terms to describe the effort to keep her daughter off West Virginia's playing fields.
“Hatred. It’s nothing but hatred,” she said. "This community is the community du jour. We have a long history of isolating marginalized parts of the community.”
Pepper-Jackson has seen some of the uglier side of the debate on display, including when a competitor wore a T-shirt at the championship meet that said, “Men Don't Belong in Women's Sports.”
“I wish these people would educate themselves. Just so they would know that I’m just there to have a good time. That’s it. But it just, it hurts sometimes, like, it gets to me sometimes, but I try to brush it off,” she said.
One schoolmate, identified as A.C. in court papers, said Pepper-Jackson has herself used graphic language in sexually bullying her teammates.
Asked whether she said any of what is alleged, Pepper-Jackson said, “I did not. And the school ruled that there was no evidence to prove that it was true.”
The legal fight will turn on whether the Constitution's equal protection clause or the Title IX anti-discrimination law protects transgender people.
The court ruled in 2020 that workplace discrimination against transgender people is sex discrimination, but refused to extend the logic of that decision to the case over health care for transgender minors.
The court has been deluged by dueling legal briefs from Republican- and Democratic-led states, members of Congress, athletes, doctors, scientists and scholars.
The outcome also could influence separate legal efforts seeking to bar transgender athletes in states that have continued to allow them to compete.
If Pepper-Jackson is forced to stop competing, she said she will still be able to lift weights and continue playing trumpet in the school concert and jazz bands.
“It will hurt a lot, and I know it will, but that’s what I’ll have to do,” she said.
Heather Jackson, left, and Becky Pepper-Jackson pose for a photograph outside of the U.S. Supreme Court in Washington, Sunday, Jan. 11, 2026. (AP Photo/Jose Luis Magana)
Heather Jackson, left, and Becky Pepper-Jackson pose for a photograph outside of the U.S. Supreme Court in Washington, Sunday, Jan. 11, 2026. (AP Photo/Jose Luis Magana)
Becky Pepper-Jackson poses for a photograph outside of the U.S. Supreme Court in Washington, Sunday, Jan. 11, 2026. (AP Photo/Jose Luis Magana)
The Supreme Court stands is Washington, Friday, Jan. 9, 2026. (AP Photo/J. Scott Applewhite)
FILE - Protestors hold signs during a rally at the state capitol in Charleston, W.Va., on March 9, 2023. (AP Photo/Chris Jackson, file)
