Is the Weight-Loss Drug Revolution Causing a Frailty Epidemic?

Chanel Robinson achieved exactly what the gold rush of blockbuster weight-loss drugs promised: She lost nearly 100 pounds, lowered her cholesterol to normal levels and reined in her polycystic ovary syndrome.

Yet, nearly three years into her journey on Mounjaro, the 30-year-old from Atlanta, Ga., is discovering the hidden costs of the slimmed-down life.

Robinson experiences muscle fatigue daily, feeling physically weak, frail and often cold. Robinson said she experiences bursts of sluggishness sporadically during the day, and has trouble with basic tasks like opening a jar. “It shouldn’t be this difficult,” she said.

GLP-1 drugs like Ozempic, Mounjaro and Zepbound have been a success for public health and the pharmaceutical companies that make them. Obesity rates are falling, the volume of food consumed in America is declining and retailers report a slump in sales of plus-size apparel. It has improved health and happiness for millions of people.

But for at least some of the 13 million Americans taking them, losing muscle along with fat is an unexpected downside that isn’t broadly discussed or immediately apparent.

The drugs can cause rapid and significant loss of lean muscle mass, up to 10%, comparable to a decade or more of aging, according to an analysis published by the American Diabetes Association.

The loss of lean tissue is similar to weight loss from dieting, but the magnitude over a short period can lead to frailty, instability and lack of coordination, doctors and researchers say. Another concern is that losing muscle could slow down patients’ metabolism, leading to weight regain.

“We are curing obesity by encouraging frailty,” said Daniel Green, principal research fellow at the University of Western Australia, who contributed to the analysis. Many taking weight-loss medications initially lose fat and feel great, but quickly start to feel weak and lethargic, he said.

Green’s research showed that the rate of muscle loss could be slowed significantly by regular strength workouts. “It should say ‘must be taken with resistance training’ on the box,” he said.

Drugmakers say weight-loss drugs should be taken only on the advice of a physician and as part of a long-term plan that includes diet and exercise.

A spokesperson for Eli Lilly, maker of Zepbound, said Food and Drug Administration guidelines say it should be used “with increased physical activity.” The spokesperson added: “Sustainable weight loss is about more than a number on a scale.”

Both Eli Lilly and Novo Nordisk said clinical trials showed users did lose some lean muscle tissue, though at far lower rates than fat. Liz Skrbkova, a spokeswoman for Novo Nordisk, said that trials for its drug Wegovy showed changes in muscle mass didn’t “significantly differ” from patients who took a placebo. Eli Lilly said users lost three times more fat weight than lean tissue.

Rayna Kingston, 30, from Denver, said her injections of Zepbound left her feeling so tired the following day that she struggled to complete anything other than basic tasks. She said she shifted her dose to a Sunday because Mondays were her least busy day. Her partner would bring her meals in bed because she felt so weak.

She stopped exercising, and said her doctor didn’t give her any guidance on strength training or muscle maintenance. “I was relying on Reddit forums to understand what was happening to my body,” she said. She got so frustrated with the fatigue she came off the medication just under two months later.

Experts say that losing muscle at such a rate can be especially dangerous for those over 50 or with osteoporosis or limited mobility as it could lead to an increased risk of injury. “Loss of muscle mass is detrimental to moving around and quality of life, but it is also not safe,” said Katsu Funai, associate professor at the University of Utah.

Elderly Americans are set to be able to get GLP-1s from Medicare from July.

There is also pushback from doctors and regulators against using weight-loss drugs as a “quick fix” to lose a bit of weight.

People who take GLP-1s regain weight four times faster than those who lose weight through lifestyle interventions, and weight regained is often mostly fat, according to a recent analysis published in the British Medical Journal. There currently are few, if any, guidelines or studies on de-prescribing the drugs, researchers say.

The nurse practitioner who prescribed Robinson the medication didn’t warn her that resistance training is essential to maintaining muscle mass, Robinson said. She said she regrets not exercising and now does Pilates once a week.

In the haste to disrupt the obesity epidemic, weight loss has been treated as the singular, undisputed metric of success, which experts say is problematic.

“People worship body weight as an outcome measure because it’s simple, quick and inexpensive,” said Green. “But what matters is fat and muscle mass, which is more expensive to measure as it requires an MRI.”

Grace Parkin, 34, a property manager from Sheffield, England, has lost 125 pounds after she started taking Mounjaro in 2024. “I don’t care about my muscle mass as long as I’m a healthy weight,” she said.

The doctor who prescribed the drug didn’t tell her to exercise, though the pharmacy that sold the medication gave her information on exercise and protein intake, she said.

She didn’t exercise and said she soon felt side effects: a “deathly cold, from the inside” likely because of the drug. Still, she vowed to keep going, saying the weight loss was worth it.

In response to some of the side effects, drug companies are hoping to develop weight-loss treatments aimed at preserving or even building lean muscle mass.

German drugmaker Boehringer Ingelheim recently said it had promising results from one such drug. Eli Lilly last September halted a trial of a similar drug.

While weight-loss medications are designed as lifelong treatments for chronic diseases, namely obesity and Type 2 diabetes, they are increasingly marketed as lifestyle fixes.

Tennis superstar Serena Williams, who used GLP-1s to slim down after having children, was featured in this year’s Super Bowl commercial promoting telehealth company Ro’s weight-loss medication.

Serena Williams holding a GLP-1 weight-loss medicine injector.

Serena Williams poses for an ad campaign for a weight-loss drug. Ro/Handout/Reuters

Women may be particularly vulnerable to the drugs’s side effects, which can also include nausea, diarrhea, migraines and rarer cases of pancreatitis.

A study last year from a university hospital in Turin, Italy, showed that women are more prone to adverse reactions to weight-loss drugs than men, including muscle loss.

Green, the researcher, said the issue is of particular concern to those taking GLP-1s recreationally and who don’t have much muscle mass to begin with. Others say a lack of oversight is compounding the issue.

“Patients are self-reporting, and telehealth companies don’t have the patient in front of them to conduct a proper medical assessment,” said Rupal Mathur, an internist in Houston whose practice specializes in weight loss.

She said medical spas are prescribing off-label drugs that don’t meet the criteria set out by the FDA that justify a prescription.

The number of people taking weight-loss drugs who are not living with obesity or Type 2 diabetes is difficult to track since it is unregulated.

However, an analysis by the FDA from 2023 found that more than half of new Ozempic and Mounjaro users didn’t have Type 2 diabetes.

Scientists are calling for more clinical trials to pin down the full effects of weight-loss drugs on muscle loss in different demographics.

“The only studies that have been done have looked at people living with obesity or Type 2 diabetes,” said Green. “That makes it all the more concerning for those using weight-loss drugs in an ad hoc or unregistered way.”

Administrative cowardice. Rampant cheating. The soaking and scamming of undergrads and grad students. Performative wokeism. Intensifying competition for international tuition dollars from an expansive China.

These are either the latest dire headlines about American higher ed or the myriad subplots of “Lords of Serendipity,” an ambitious new novel by Randy Boyagoda. Unlike most campus fiction, its scope extends well beyond the cloister of the liberal arts classroom to whammy the entire university system, from its financial model to its function within a globalized economy. Along the way, it skewers its lightning-rod targets with a precision too sharp to be considered entirely fictional.

That its author is not only well-versed in satire, having written four other novels in the genre, but is also a professor of English at the University of Toronto and an experienced college administrator, further blurs the lines between comic fiction and brutal fact. It’s the kind of no-holds-barred book only a consummate insider would know to write—but only one who is also conveniently outside the American university system could get away with writing.

“This is someone who’s got the inside dope on what can go on at universities, especially with international students, and what kind of con games are going on,” said Margaret Atwood, a friend and fellow Torontonian.

The novel, like Boyagoda himself, is often very funny—even as the dilemmas its characters face read as tragedy. Its cast includes the bickering members of a Sri Lankan hotel cleaner’s family, insecure American freshmen, dead-end third-tier college professors and their highflying Ivy League counterparts and dispirited university functionaries. An old-fashioned Dickensian tale, it sweeps across continents and campuses, from a classic liberal-arts college to a stand-in for Harvard University to an urban technical school to the dilapidated buildings of a state-run university in Sri Lanka.

“I’m a joyful person,” Boyagoda said in an interview, though he prefers to see his outlook on academia as “hopeful” rather than optimistic. He smiles and laughs frequently. He bikes everywhere. He derives energy from his students and from his four daughters, ages 14 to 20. They help him and his American wife, Anna, also an educator, care for Boyagoda’s father, an immigrant from Sri Lanka who has dementia and lives with the family.

Randy Boyagoda speaks at a panel discussion. — Randy Boyagoda taking part in a panel discussion at the University of Toronto in 2024. Polina Teif/University of Toronto

The germ of the novel came to Boyagoda during the pandemic, when he was serving as a vice-dean. An urban legend was circulating about a statistics grad student selling passing grades to international students. The cheating scheme itself may well have been apocryphal, but it felt tantalizingly plausible.

“As a novelist, it stayed with me,” Boyagoda said. “Who would sell grades for a stats course? Why would someone buy grades? What’s motivating them? Why wouldn’t the university be doing something about it?” What he didn’t want to do, he explained, was write “another novel about a creative writing professor and his drama with students.”

In addition to writing novels—the first of which was a finalist for Canada’s prestigious Giller Prize; he’s written eight books in total—Boyagoda teaches literature full-time. For his students next semester, kids raised in a purportedly “post-literature era,” he’s assigning three 700-page novels, he noted mischievously, books by George Eliot, Ralph Ellison and Kiran Desai.

On RateMyProfessors, students remark on Boyagoda’s heavy assignments, tough grading and distaste for cellphones, but also hail his “comedy.” When alerted to these reviews, Boyagoda laughed. “Guilty as charged,” he said.

“Randy’s one of those people in academia who is very well educated but doesn’t have an ounce of superiority about him,” said John Irving, who frequently guest lectures in Boyagoda’s classroom. “It’s amazing to see how willing students are to talk in his classrooms, how little afraid they feel of being mocked or put down—he gets complete candor out of them.”

Negotiating competing interests seems to come naturally to him. Like many college campuses, after the Oct. 7 Hamas attack on Israel, the University of Toronto was embroiled in protests, encampments and discord; part of the school’s response was to convene a working group on civil discourse. Boyagoda was put in charge, serving for two years. It’s the kind of thankless task many professors would flee from, but Boyagoda relished the prospect and thinks the group, which is ongoing, made progress.

He has since pivoted to another formidable academic concern: the waning prestige of the humanities. In July, Boyagoda became the director of the Jackman Humanities Institute and special advisor on the humanities to the dean of arts and science. This fall, he is starting a series of gatherings he calls the Dead Book Club. (Dead writers feature heavily among his favorites: St. Augustine, Dante, William Faulkner, Evelyn Waugh, Saul Bellow.)

“The goal is to encourage students to read for its own sake and have conversation for its own sake,” Boyagoda said. “The importance of the humanities will be revealed to those who participate.”

Illustration of the book cover for "Lords of Serendipity" by Randy Boyagoda, depicting a woman wearing a hat with various buildings on top, against a blue background with a white airplane.

“Lords of Serendipity,” which publishes next week, reflects Boyagoda’s commitment to the pursuit of knowledge: “I’m supposed to say I learn more from my students than they do from me, but no,” Boyagoda said. “I enjoy sharing my excitement and joy about literature and ideas. There are these moments when you are teaching and you can see someone’s face change because they didn’t know something and then they did. That moment when you’re actually watch someone enlarge themselves is deeply satisfying.”

In literary circles, Boyagoda is often referred to as a Catholic novelist, a description he embraces. “A novelist willing to give shape and voice to contemporary religious experience is needed,” Boyagoda said. “I understand myself as a Catholic novelist, provided that I’m not only a Catholic novelist, I’m also a South Asian novelist and I’m a Canadian novelist. I don’t want to be captive to one label.”

His characters, he said, are subjected to what he calls “Graham Greene character situations.”

“They are trying to do good in a fallen world and realize the most they can do is less harm than someone else would do in that same role,” he explained. “They have to accept they are complicit in something that provides some good thing to others. It’s a very Graham Greene way of thinking about sacrifice.”

The campus green they inhabit is a febrile zone in which lofty ideals and cynicism regularly collide. It’s a place where a traditional holiday college celebration is now an occasion for political protest. Kids freely police one another inside and out of the classroom with social media their constant, ready weapon of choice. International students, knowing their family’s financial futures hinge on their degrees, operate in terror of failure and deportation.

Early readers of the book include Gary Shteyngart and Junot Diaz, both of whom have taught at universities and written comic novels. They each contacted Boyagoda midway through to say, in essence, “You nailed it.”

As biting as “Lords of Serendipity” can be, Boyagoda’s faith in higher education remains undaunted.

“It’s absurd that we live in societies that make the decision to take people between the ages of 18 and 22, when they are most physically capable of contributing to our nations and communities, and tell them, ‘Go away for four years, and read and learn and have conversations,’” he said. “I want students to be aware of what an incredible privilege that is.”

Corrections & Amplifications
Randy Boyagoda is a special advisor on the humanities to the dean of arts and science at the University of Toronto. An earlier version of this article incorrectly said he is a special adviser to the dean of humanities. (Corrected on Sept. 2)

Is the Weight-Loss Drug Revolution Causing a Frailty Epidemic?

As millions flock to GLP-1s, doctors warn the drugs can cause rapid and significant muscle loss.

Randy Boyagoda’s new novel, “Lords of Serendipity,” delivers a biting satire of cheating, politics and dysfunction across modern universities.