Serena Williams and the coming reckoning with GLP-1s and performance enhancement

Serena Williams is back.

Teaming up with rising Canadian teenager Victoria Mboko for a straight-sets win over the No. 3 seeds in women’s doubles at the Queen’s grass-court tournament in London, Williams sent a message to the tennis world that it may be in for an interesting summer.

Williams’ comeback comes just under one year after she decided she had something else to tell the world.

Last summer, the 23-time Grand Slam singles champion said she had been taking Zepbound, one of the new generation of drugs which are designed to treat diabetes, but can also help people lose weight: GLP-1s.

Williams, 44, said that she made the decision after trying just about every other avenue. She had not wanted to take “the shortcut,” she said on Oprah Winfrey’s podcast last August, but, Williams said, getting to where she wanted to be after her two pregnancies was not working through training alone.

“I couldn’t beat the weight. It was the one opponent I couldn’t beat,” Williams, who manages her treatment through Ro, a telehealth company for which she serves as a paid ambassador, said.

Charles Barkley, the NBA Hall of Famer and TV analyst, is also an ambassador. Williams’ husband, Alexis Ohanian, a founder of Reddit, is a major investor in Ro, which displayed adverts during U.S. broadcast of her comeback match on Tennis Channel.

At the time, Williams had not played a professional match in nearly three years. She had snuffed out talk of a comeback, busy being Serena Williams, one of the greatest tennis players and athletes of all time, a star of business and pop culture as much as the tennis court.

That all changed last week, when Williams announced that she would play doubles at one of the main tuneups for Wimbledon, which she has won seven times. No one expects her comeback to stop at Queen’s, or with doubles, though she has not directly committed to playing singles yet.

Immediately, Williams reclaimed her position as the most magnetic star in the sport. She also became by far the most prominent athlete to compete at the highest level of their sport having taken GLP-1 drugs, which anti-doping authorities have been monitoring since 2024.

They are not a prohibited substance, nor classed as a performance-enhancing drug. They may never be. Williams’ communication team declined an interview for this story, and to express her views on the debate about whether the drugs could be banned.

Williams, who has always been a story unto herself, returns to the arena she dominated as a character in a larger debate hanging over the world of sports.

Semaglutides and tirzepatides, the two main classes of GLP-1 drug, have been on the World Anti-Doping Agency (WADA) monitoring program since 2024. They work by mimicking the behavior of glucagon, a naturally occurring hormone that triggers the pancreas to release insulin, slow digestion and reduce appetite and hunger.

People who take GLP-1s — Glucagon-Like Peptides — report significant reduction in “food noise,” the part of their mind that thinks about the next snack or meal. The reduction in food intake can lead to significant weight loss.

There is no timetable on the WADA process for establishing whether GLP-1s are performance-enhancing, a spokesperson for the organization said. Tennis anti-doping protocol is managed by the International Tennis Integrity Agency (ITIA), but as an Olympic sport, WADA oversees its compliance with its code.

“The WADA List Expert Advisory Group has discussed their status, as well as other substances of the same class,” the statement said.

“Semaglutide and tirzepatide were added to the Monitoring Program to track patterns of use in sports in and out of competition. The Monitoring Program includes substances which are not on the Prohibited List, but that WADA wishes to monitor in order to detect potential patterns of misuse in sport.”

A spokesperson for Novo Nordisk said in a statement that the pharmaceutical company, which produces and distributes GLP-1s, agreed with WADA’s decision to monitor GLP-1 usage: “We are supportive of the WADA recommendation, and we strongly discourage use/promotion outside the indicated population and approved label.”

A spokesperson for Eli Lilly, another company that manufactures and distributes GLP-1s, said: “Zepbound (tirzepatide) and Foundayo (orforglipron) are indicated for use, along with diet and exercise, for adults with obesity or overweight and a weight-related comorbidity. Lilly does not promote or encourage use of any Lilly medicine outside of its FDA-approved indication. Treatment decisions should be made by patients and their healthcare providers.”

To land on the banned list, a substance has to satisfy two of three criteria: The potential to enhance sport performance; the potential to be a risk to athletes’ health; the potential to violate what WADA defines in its code as the “spirit of sport.”

There is a divide in the anti-doping world over whether violating the “spirit of sport” is too vague a criterion, and that enforcement should be based on science alone. For now, though, taking what WADA deems a shortcut in training can contribute to a substance landing on the banned list.

It has shown increasing concern about the role of weight-loss drugs in sports. Minutes of a meeting of WADA’s Health and Research Committee last August show a discussion of “whether a new class addressing all types of weight management substances should be created, not only for weight category sports but also weight-sensitive ones (e.g. gymnastics, figure skating, cycling).”

The concern is that as companies develop GLP-1s to become faster-acting and more effective, athletes could use them as a shortcut for training. That’s where the violation of the “spirit of sport” could come into play.

The question is whether enough experts and officials ultimately agree that GLP-1s will offer a shortcut equivalent to substances like diuretics, which are pills that cause the kidneys to put extra salt and water into urine.

They are on the banned list because by diluting urine they can make it harder to detect actual performance-enhancing drugs through urine tests, but they can also help athletes in sports like boxing and mixed martial arts make weight before a bout.

Serena Williams last year became an ambassador for Ro, a telehealth company that distributes GLP-1s. (Richard B. Levine / SIPA)

GLP-1 drugs act much more slowly, with the goal of a more permanent result. Losing weight with the assistance of one can take months.

When Williams began to do research into GLP-1 drugs, how they worked, and why no matter how much training she did, she wasn’t going to be able to lose the weight she wanted to, she felt she was not taking any kind of shortcut.

Instead, she told Winfrey, she was assisting something with her biology that wasn’t working, a view shared by weight and diet specialists.

In her late career, Williams felt her bid for yet more tennis records was compromised by joint issues associated with her weight.

“My joints are so much lighter,” she told Winfrey.

How GLP-1s cause weight loss may further complicate whether they can be considered performance-enhancing.

Fat loss is the main contributor. But studies of GLP-1 patients have shown that muscle loss also occurs, which for athletes, would do the opposite of enhancing performance.

The muscle-wasting effects have prompted scientists to try to find a drug to counteract them. In 2023, VERU, a Miami-based pharmaceutical company, announced that one of its experimental drugs, Ostarine, also known as enobosarm, had shown some early success in clinical trials to prevent muscle-wasting among elderly patients and people suffering from diseases such as cancer.

It is currently conducting trials that could ultimately lead to its use in concert with GLP-1 drugs (a process known as adjunctive therapy) so patients don’t lose lean muscle. That option won’t be available to athletes. Ostarine, which athletes can and do purchase in the black market, is on WADA’s Prohibited List.

“It should be on the list and banned from sport because it’s very effective,” Mitchell Steiner, chief executive of VERU said during an interview. “It’s a performance drug. Our job is to get the right indication and show the safety in a controlled setting.”

GLP-1 manufacturers may eventually tweak the molecular structure of the drugs to minimize muscle loss. That could tip the scale of any judgment on their ability to enhance performance.

“I think what you’re going to start seeing is new products being introduced to the market that actually have less of those side effects, which then would be more advantageous for athletes,” said Matthew Fedoruk, the chief science officer at the U.S. Anti-Doping Agency (USADA).

“So this is a growing threat that I think needs to be monitored closely.”

If GLP-1s do become prohibited, athletes could theoretically apply for a therapeutic use exemption (TUE), which allows them to take a drug if it is treating a legitimate medical condition, and does not meaningfully enhance their performance.

These can be common, for instance, among endurance athletes who suffer from asthma and need to take low-grade steroids through an inhaler. In the case of GLP-1 drugs, the most likely exemption could be for diabetes.

Serena Williams’ first match of her comeback drew plenty of attention at Queen’s, a grass-court event held in west London. (Paul Harding / Getty Images)

In the months after she gave birth to her second child in 2023, Williams quickly found herself fielding questions about whether she would consider a comeback.

In her August 2022 essay in “Vogue” announcing her “evolving away” from tennis, Williams wrote that she did not have the opportunity to play on with the freedom of someone like her friend, the great NFL quarterback Tom Brady, whose then-wife had three children during his career, which lasted, uninterrupted — barring one change of heart 12 months from the end — until he was 45.

Fitness never stopped being a part of her routine. Eventually, she made her way back to the tennis court. Through last year, there were rumors that she was considering a comeback.

In the fall, Williams’ name appeared in the sport’s anti-doping testing pool, the first step in a potential comeback.

Players who leave tennis and remove themselves from the pool have to return to it for six months before becoming eligible to play in tournaments. Once they are in the testing pool, they have to commit to being at a certain location for one hour each day and be subject to random drug testing.

In December, Williams took to social media to tell the world it was much ado about nothing: She was not coming back.

A few months later, on “Today,” she dodged questions about a return from Savannah Guthrie, but refused to take the opportunity to say it wasn’t happening.

Then, last week, it did. Twenty-four hours after she and Queen’s Club announced the comeback, she released photos of herself in the bespoke Nike kits she plans to wear on the court.

Then, on Tuesday, she played. She cracked serves and whipped forehands and connected on touch volleys and overheads. She walked the court with that majestic presence that was long her trademark. Her two daughters sat courtside, taking it all in with the thousands of others who packed the main stadium, as Williams and Mboko defeated New Zealand’s Erin Routliffe and Nicole Melichar-Martinez of the U.S. 7-6(2), 6-2.

“I wish I had done this while I was still playing,” Williams told Winfrey of taking GLP-1s, when her comeback was still just an idea. “It would have made such a big difference for me and my career.”

Now, she is finding out how right she might have been.