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We Know Where New Weight Loss Drugs Came From, but Not Why They Work

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We Know Where New Weight Loss Drugs Came From, but Not Why They Work

Every so often a drug comes along that has the potential to change the world. Medical specialists say the latest to offer that possibility are the new drugs that treat obesity — Ozempic, Wegovy, Mounjaro and more that may soon be coming onto the market.

It’s early, but nothing like these drugs has existed before.

“Game changers,” said Jonathan Engel, a historian of medicine and health care policy at Baruch College in New York.

Obesity affects nearly 42 percent of American adults, and yet, Dr. Engel said, “we have been powerless.” Research into potential medical treatments for the condition led to failures. Drug companies lost interest, with many executives thinking — like most doctors and members of the public — that obesity was a moral failing and not a chronic disease.

While other drugs discovered in recent decades for diseases like cancer, heart disease and Alzheimer’s were found through a logical process that led to clear targets for drug designers, the path that led to the obesity drugs was not like that. In fact, much about the drugs remains shrouded in mystery. Researchers discovered by accident that exposing the brain to a natural hormone at levels never seen in nature elicited weight loss. They really don’t know why.

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“Everyone would like to say there must be some logical explanation or order in this that would allow predictions about what will work,” said Dr. David D’Alessio, chief of endocrinology at Duke, who consults for Eli Lilly among others. “So far there is not.”

Although the drugs seem safe, obesity medicine specialists call for caution because — like drugs for high cholesterol levels or high blood pressure — the obesity drugs must be taken indefinitely or patients will regain the weight they lost.

Dr. Susan Yanovski, a co-director of the office of obesity research at the National Institute of Diabetes and Digestive and Kidney Diseases, warned that patients would have to be monitored for rare but serious side effects, especially as scientists still don’t know why the drugs work.

But, she added, obesity itself is associated with a long list of grave medical problems, including diabetes, liver disease, heart disease, cancers, sleep apnea and joint pain.

“You have to keep in mind the serious diseases and increased mortality that people with obesity suffer from,” she said.

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The drugs can cause transient nausea and diarrhea in some. But their main effect is what matters. Patients say they lose constant cravings for food. They find themselves satisfied with much smaller portions. They lose weight because they naturally eat less — not because they burn more calories.

And results from a clinical trial reported last week indicate that Wegovy can do more than help people lose weight — it also can protect against cardiac complications, like heart attacks and strokes.

But why that happens remains poorly understood.

“Companies don’t like the term trial and error,” said Dr. Daniel Drucker, who studies diabetes and obesity at the Lunenfeld-Tanenbaum Research Institute in Toronto and who consults for Novo Nordisk and other companies. “They like to say, ‘We were extremely clever in the way we designed the molecule,” Dr. Drucker said.

But, he said, “They did get lucky.”

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In the 1970s, obesity treatments were the last thing on Dr. Joel Habener’s mind. He was an academic endocrinologist starting his own lab at Harvard Medical School and looking for a challenging, but doable, research project.

He chose diabetes. The disease is caused by high blood sugar levels and is typically treated with injections of insulin, a hormone secreted by the pancreas that helps cells store sugar. But an insulin injection makes blood sugar plummet, even if levels are already low. Patients have to carefully plan injections because very low blood sugar levels can result in confusion, shakiness and even a loss of consciousness.

Two other hormones also play a role in regulating blood sugar — somatostatin and glucagon — and little was known then about how they are produced. Dr. Habener decided to study the genes that direct cells to make glucagon.

That led him to a real surprise. In the early 1980s, he discovered a hormone, GLP-1, that exquisitely regulates blood sugar. It acts only on insulin-producing cells of the pancreas, and only when blood sugar rises too high.

It was perfect, in theory, as a targeted treatment to replace sledgehammer-like insulin injections.

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Another researcher, Dr. Jens Juul Holst at the University of Copenhagen, independently stumbled on the same discovery.

But there was a problem: When GLP-1 was injected, it vanished before reaching the pancreas. It needed to last longer.

Dr. Drucker, who led the GLP-1 discovery efforts on Dr. Habener’s team, labored for years on the challenge. It was, he said, “a pretty lonely field.”

When he applied to the Endocrine Society to give talks, he found himself scheduled at the very end of the last day of the annual meetings.

“Everyone had left for the airport — people were taking down the exhibits,” he said.

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From the late 1980s to the early 1990s, he spoke to nearly empty auditoriums.

Success came from a chance discovery that was not appreciated at the time.

In 1990, John Eng, a researcher at the Veterans Affairs medical center in the Bronx, was looking for interesting new hormones in nature that might be useful for medications in people.

He was drawn to the venomous Gila monster when he learned that it somehow kept its blood sugar levels stable when it did not have much to eat, according to a report from the National Institutes of Health, which funded his work. So Dr. Eng decided to search for chemicals in the lizards’ saliva. He found a variant of GLP-1 that lasted longer.

Dr. Eng told The New York Times in 2002 that the V.A. had declined to patent the hormone. So Dr. Eng patented it himself and licensed it to Amylin Pharmaceuticals, which began testing it as a diabetes drug. The drug, exenatide or Byetta, went on sale in the United States in 2005.

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But Byetta had to be injected twice a day, a real disincentive to its use. Drug company chemists sought even longer-lasting versions of GLP-1.

At Novo Nordisk, chemists began by using a well-known trick. They loosely attached GLP-1 to a blood protein that kept it stable enough to remain in circulation for at least 24 hours. But when GLP-1 slips off the protein, enzymes in the blood quickly degrade it. So chemists had to alter the hormone’s building blocks — a chain of amino acids — to find a more durable variant.

After tedious trial and error, Novo Nordisk produced liraglutide, a GLP-1 drug that lasted long enough for daily injections. They named it Saxenda, and the F.D.A. approved it as a treatment for diabetes in 2010.

It had an unexpected side effect: slight weight loss.

Obesity had become a dead end in the pharmaceutical industry. No drug that was tried worked very well, and every one that led to even modest weight loss had serious side effects.

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For a flickering moment in the late 1990s, there was hope when Dr. Jeffrey Friedman at Rockefeller University in New York found a hormone that told the brain how much fat was on the body. Lab mice genetically modified to have none of the hormone ate voraciously and grew enormously fat. Researchers could fine-tune an animal’s weight by altering how much of the hormone it got.

Dr. Friedman named the hormone leptin. Amgen bought the rights to leptin and, in 1996, began testing it in people. They did not lose weight.

Dr. Matthias Tschöp at Helmholtz Munich in Germany tells of the frustration. He left academia three decades ago to work at Eli Lilly in Indianapolis, excited by leptin and determined to use science to find a drug for weight loss.

“I was so inspired,” Dr. Tschöp said.

When leptin failed, he tried a different gut hormone, ghrelin, whose effects were the opposite of leptin’s. The more ghrelin an animal had, the more it would eat. Perhaps a drug that blocked ghrelin would make people lose weight.

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“Again, it wasn’t that simple,” said Dr. Tschöp, who left Lilly in 2002.

The body has so many redundant circuits of interacting nerve impulses and hormones to control weight that tweaking one simply did not make a difference.

And there was another obstacle, noted Dr. Tschöp’s former colleague at Lilly, Dr. Richard Di Marchi, who also was an executive at Novo Nordisk.

“There was very little interest in the industry in doing this,” said Dr. Di Marchi, now at Indiana University. “Obesity was not thought to be a disease. It was looked at as a behavioral problem.”

Novo Nordisk, which today has 45.7 percent of the global insulin market, thought of itself as a diabetes company. Period.

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But one company scientist, Lotte Bjerre Knudsen, could not stop thinking about tantalizing results from studies with liraglutide, the GLP-1 drug that lasted long enough to be injected just once a day.

In the early 1990s, Novo researchers, studying rats implanted with tumors of pancreas cells that produced copious amounts of glucagon and GLP-1, noticed that the animals had nearly stopped eating.

“These rats, they starved themselves,” Dr. Knudsen said in a video series released by the Novo Nordisk Foundation. “So we kind of knew there was something in some of these peptides that was really important for appetite regulation.”

Other studies by academic researchers found that rats lost their appetites if GLP-1 was injected into their brains. Human subjects who got an intravenous drip of GLP-1 ate 12 percent less at a lunch buffet than those who got a placebo.

So why not study liraglutide as both a diabetes drug and an obesity drug, Dr. Knudsen asked .

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She faced resistance in part because some company executives were convinced that obesity resulted from a lack of willpower. One of the champions of investigating GLP-1 for weight loss, Lars Rebien Sorensen, chairman of the board at Novo Nordisk, said in the video posted by the company’s foundation that he “had to spend half a year convincing my C.E.O. that obesity is not just a lifestyle condition.”

Dr. Knudsen also noted that the company’s business division had struggled with the idea of promoting liraglutide for two distinct purposes.

“It’s either diabetes, or it’s a weight loss,” she recalled in the foundation video series.

Finally, after liraglutide was approved in 2010 for diabetes, Dr. Knudsen’s proposal to study the drug for weight loss moved forward. After clinical trials, the F.D.A. approved liraglutide, or Saxenda, for obesity in 2014. The dose was about twice the diabetes dose. Patients lost about 5 percent of their weight, a modest amount.

But Dr. Martin Holst Lange, executive vice president of development at Novo Nordisk, said in a telephone interview that it was at least as good as other weight-loss drugs, and without side effects like heart attacks, strokes and death.

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“We were super excited,” he said.

Despite the progress on weight loss, Novo Nordisk continued to focus on diabetes, trying to find ways to make a longer-lasting GLP-1 so patients would not have to inject themselves every day.

The result was a different GLP-1 drug, semaglutide, that lasted long enough that patients had to inject themselves only once a week. It was approved in 2017 and is now marketed as Ozempic.

It also caused weight loss — 15 percent, which is three times the loss with Saxenda, the once-a-day drug, although there was no obvious reason for that. Suddenly, the company had what looked like a revolutionary treatment for obesity.

But Novo Nordisk could not market Ozempic for weight loss without F.D.A. approval for that specific use.

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In 2018, a year after Ozempic’s approval for diabetes, the company started a clinical trial. In 2021, Novo Nordisk got approval from the F.D.A. to market the same drug for obesity with a weekly injection at a higher maximum dose. It named the drug Wegovy.

But even before Wegovy was approved, people had begun taking Ozempic for obesity. Novo Nordisk, in its Ozempic commercials, mentioned that many taking it lost weight.

Hinting turned out to be more than enough. Soon, said Dr. Jeffrey Mechanick, an endocrinologist at Mount Sinai’s Icahn School of Medicine, patients latched onto Ozempic. Doctors prescribed it off label for those who did not have diabetes.

“There was a little bit of gaming going on,” Dr. Mechanick said, with some doctors coding patients as having pre-diabetes to help them get insurance coverage.

By 2021, fed by social media, a general frenzy for weight loss and aggressive marketing by Novo Nordisk, the news that Ozempic made people lose weight had reached a tipping point, said Dr. Caroline Apovian, a co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and a consultant for Novo Nordisk and other companies. Ozempic was on everyone’s lips, even though Wegovy was the drug approved that year for obesity.

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But Wegovy caught up.

In July, doctors in the U.S. wrote about 94,000 prescriptions a week for Wegovy compared with about 62,000 a week for Ozempic. Wegovy is in such demand, though, that the company is unable to make enough, its spokeswoman Ambre James-Brown said. So for now, while it ramps up production, the company sells the drug only in Norway, Denmark, Germany and the United States. And at pharmacies in those countries, shortages are frequent.

And Dr. Apovian, like many other obesity medicine specialists, is now booked with patients a year in advance.

The reason Ozempic and Wegovy are so much more effective than Saxenda remains a mystery. Why should a once-a-week injection produce much more weight loss than a once-a-day injection?

The drugs, said Randy Seeley, an obesity researcher at the University of Michigan, are not correcting for a lack of GLP-1 in the body — people with obesity make plenty of GLP-1. Instead, the drugs are exposing the brain to hormone levels never seen in nature. Patients taking Wegovy are getting five times the amount of GLP-1 that they would produce in response to a Thanksgiving dinner, Dr. Seeley said.

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And, he added, in the brain, “the drugs go to unusual places.” They are not just going to areas thought to involve control overeating.

“If you were designing a drug, you would say that’s a bad idea,” said Dr. Seeley, who has consulted for Novo Nordisk and Eli Lilly, among others. Drug designers try for precision — a drug should go only to the cells where it is needed.

GLP-1, because of its chemical structure, should not even get into some areas of the brain where it slips in.

“Nobody understands that,” Dr. Seeley said.

Wegovy, though, is just the start.

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Lilly’s diabetes drug, tirzepatide or Mounjaro, is expected to get F.D.A. approval for obesity this year. It hooks GLP-1 to another gut hormone, GIP.

GIP, on its own, produces, at best, a modest weight loss. But the two-hormone combination can allow people to lose a median of about 20 percent of their weight.

“No one fully understands why,” Dr. Drucker said.

Lilly has another drug, retatrutide, that, while still in early stages of testing, seems to elicit a median 24 percent weight loss.

Amgen’s experimental drug, AMG 133, could be even better, but is even more of a puzzle. It hooks GLP-1 to a molecule that blocks GIP.

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There is no logical explanation for why seemingly opposite approaches would work.

Researchers continue to marvel at these biochemical mysteries. But doctors and patients have their own takeaway: The drugs work. People lose weight. The constant chatter in their brains about food and eating is gone.

And, while the stigma of obesity and the cultural stereotype that obese people aren’t trying hard enough to lose weight endures, some experts are optimistic. Now, they say, patients no longer have to blame themselves or feel like failures when they can’t lose weight.

“The era of ‘just go out and diet and exercise’ is now gone,’” said Dr. Rudolph Leibel, a professor of diabetes research at Columbia University Irving Medical Center. “Now clinicians have tools to address obesity.”

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The Tijuana River smells so bad, the CDC is coming to investigate

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The Tijuana River smells so bad, the CDC is coming to investigate

San Diego County residents will have an opportunity to share their pollution concerns about the Tijuana River when officials from the Centers for Disease Control and Prevention arrive later this month to conduct a health survey.

This is the first time that a federal agency is investigating the potential harm caused by millions of gallons of raw sewage pouring through the Tijuana River that have caused beach closures of more than 1,000 days. Residents living near the river say they have been suffering unexplained illnesses, including gastrointestinal issues and chronic breathing problems, because of the stench of hydrogen sulfide.

“We’re continuing to lean in and listen in on what our community residents are feeling,” said Dr. Seema Shah, the interim deputy public health officer with San Diego County. Supervisor Nora Vargas first wrote to the CDC back in May, formally asking the U.S. Department of Health and Human Services to look into the health complaints.

This week, the county began reaching out to thousands of residents to inform them that the CDC is coming in the hope that they will be more receptive to answering questions. “This is our chance to be able to communicate [pollution concerns] on a national level,” Shah added.

As part of what the CDC calls a Community Assessment for Public Health Emergency Response, 210 households will be surveyed about their mental and physical health, as well as the pollution’s effects on property values. The families will be randomly selected from 30 clusters of neighborhoods where San Diego County has identified air pollution complaints in the Tijuana River Valley.

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Around 30 officials from the CDC and 50 graduate student volunteers from San Diego State University’s School of Public Health will be going door to door to conduct interviews with local residents over a three-day period. Here are the times when the survey will be conducted:

  • Thursday, Oct. 17, 2024, from 2 p.m. to 7 p.m.
  • Friday, Oct. 18, 2024, from 2 p.m. to 7 p.m.
  • Saturday, Oct. 19, 2024, from 10 a.m. to 7 p.m.

The goal is to accommodate people’s schedules and, officials hope, catch them after work, Shah said. The volunteers are helping to bridge the language barriers with Spanish-speaking families.

“A lot of students, many of whom are bilingual, are from the community themselves,” said Paula Granados, an associate professor at San Diego State University’s School of Public Health, who’s been testing the Tijuana River for contaminants over the past month. “Our students are super excited. They want to help.”

The CDC could take weeks to months to release even the preliminary results from the survey, but for longtime residents like Bethany Case, this renewed attention already feels like a breath of hope.

“I just really want [this survey] to inform policy so that we don’t have to worry about our kids being sick,” said Case, the mother of two who’s lived in Imperial Beach for 16 years. For seven years she’s been an activist fighting to clean up the river as a volunteer with Surfrider, a nonprofit that works to preserve ocean access and cleanliness.

“I’m hoping that their survey shows that oftentimes it doesn’t just smell like sewage,” Case added. She doesn’t want the focus on the sewage to distract from the industrial waste that is dumped into the river that could be making people ill. “Oftentimes it smells like a chemical, it smells like a bite in the air, it burns your sinuses.”

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Granados said the CDC’s survey is only a snapshot of what was going on when the data were collected, and conditions could worsen for residents when rainy seasons flood the river once more. Granados wants residents to know that even if they aren’t picked to respond to this survey, SDSU will be conducting its own yearlong survey that they can answer multiple times at tjriver.sdsu.edu.

“There’s research that’s still ongoing,” Granados said, and all that data will help policy decisions in the future. “We’re just committed to the long haul, whatever it takes to support the community.”

The county and other federal and state representatives have been working to raise awareness around the pollution to a national level.

Next week, the San Diego County Board of Supervisors will consider a proposal by Supervisor Terra Lawson-Remer to petition the Environmental Protection Agency to label the Tijuana River a Superfund site in need of remediation.

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'More serious than we had hoped': Bird flu deaths mount among California dairy cows

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'More serious than we had hoped': Bird flu deaths mount among California dairy cows

As California struggles to contain an increasing number of H5N1 bird flu outbreaks at Central Valley dairy farms, veterinary experts and industry observers are voicing concern that the number of cattle deaths is far higher than anticipated.

Although dairy operators had been told to expect a mortality rate of less than 2%, preliminary reports suggest that between 10% and 15% of infected cattle are dying, according to veterinarians and dairy farmers.

“I was shocked the first time I encountered it in one of my herds,” said Maxwell Beal, a Central Valley-based veterinarian who has been treating infected herds in California since late August. “It was just like, wow. Production-wise, this is a lot more serious than than we had hoped. And health-wise, it’s a lot more serious than we had been led to believe.”

A total of 56 California dairy farms have reported bird flu outbreaks. At the same time, state health officials have reported two suspected cases of H5N1 infections among dairy workers in Tulare County, the largest dairy-producing county in the nation. With more than 600,000 dairy cows, the county accounts for roughly 30% of the state’s milk production.

Beal’s observations were confirmed by others during a Sept. 26 webinar for dairy farmers that was hosted by the California Dairy Quality Assurance Program — an arm of the industry-funded California Dairy Research Foundation. A summary of the findings and observations was reported in a newsletter published earlier this week by the program.

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Beal, along with Murray Minnema, another Central Valley veterinarian, and Jason Lombard, a Colorado State University veterinarian, described their observations and data to dairy farmers to help them anticipate the signs of, and treatments for, the virus.

The webcast was not made available to The Times.

“The animals really don’t do well,” Beal told The Times.

He said the infected cows he has seen are not dissimilar to people who are suffering from a typical flu: “They don’t look so hot.”

He and others think the recent heat may be a factor.

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Since the end of August, the Central Valley has suffered multiple heat waves, with daytime temperatures exceeding 100 degrees.

“Heat stress is always a problem in dairy cattle here in California,” he said. “So you take that, you add in this virus, which does have some affinity for the respiratory tract … we always see a little bit of snotty noses and heavy breathing in animals that are affected … and for some of them, just the stress takes them.”

Indeed, most of the deaths are not directly the result of the virus, he said, but are “virus adjacent.” For instance, he has seen a lot of bacterial pneumonia, which is likely the result of the cow’s depressed immune system, as well as bloat.

He said that when the cows aren’t feeling well, they often don’t eat.

“The digestive tract, or rumen, basically requires movement. There has to be things moving out of that rumen constantly in order for the pH balance and microbiome to stay where it should be,” he said. So, when they’re not eating, things in the digestive tract stagnate.

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That, in turn, causes them to “asphyxiate because their diaphragm has too much pressure on it.”

In addition, he and others are seeing a lot of variation in the duration of illness.

While early reports had suggested the virus seemed mild and lasted only about a week or two, others are seeing it last several weeks. According to the industry newsletter, at one dairy, cows were shedding virus 14 days before they showed clinical signs of illness. It then took another three weeks for the cows to get rid of the virus.

They’re also noticing the virus is affecting larger percentages of herds — in some cases 50%-60% of the animals. This is much more than the 10% that had been previously reported.

Some say the actual rate may be even higher.

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“I would speculate infection is even higher; 50-60% are showing clinical signs due to heat stress or better herd monitoring earlier in infection. Unfortunately, few or no herds have been assessed retrospectively through serology testing to determine actual infection rates,” said John Korslund, a retired U.S. Department of Agriculture veterinarian epidemiologist.

Cows are also not returning to 100% production after they’ve cleared the virus, said Beal. Instead, he and others say it’s closer to 60%-70%.

“There’s going to be some animals that are removed from the herd, because they never seem to come back,” he said.

Beal said his firsthand observations have really challenged his notions about the disease, which has so often been described as mild and insignificant.

“Once I saw it myself, I said, this is something I need to communicate with my clients about … this is not something that is just a joke at the dinner table,” he said. “I didn’t want people to not take it seriously, because I see what it is doing to the animals, and it is rough to see — as an animal caretaker, as a veterinarian like myself — it’s just not something that’s enjoyable. It’s more serious than we had been led to believe.”

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He said he is working hard with Central Valley farmers to treat the animals — largely by making sure the cattle are adequately hydrated. He also treats sick cows with a medication similar to aspirin, to reduce fever, pain and discomfort.

He said the treatment is pretty effective, and seems to be helping.

Others are not surprised H5N1 is becoming more severe in cows.

“As I’ve said since we first learned of the outbreak in dairy cows, nothing we’ve learned about this virus is new or unexpected,” said Rick Bright, a virologist and former head of the U.S. Biomedical Advanced Research and Development Authority. “It’s behaving exactly as we’ve come to know of this virus over the past 25 years. It’s spreading very efficiently now among mammals, and it’s mutating and adapting to mammals as it does.”

He credited state health officials and veterinarian for “being more forthcoming and transparent with their data” than other states, and said this may be the reason the virus seems to be hitting California cows so hard.

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“This virus is out of control. It is time for urgent and serious leadership and action to halt further transmission and mutation,” Bright said. “The concept of letting it burn out through food animals, with unmonitored voluntary testing, has failed. There are pandemic playbooks that we need to dust off and begin to implement.”

In the meantime, officials continue to reassure the public about the safety of the nation’s dairy supply. They say pasteurization inactivates the virus. They also warn people to stay away from raw milk.

Beal noted one of the sentinel signs that a farm has been infected is dead barn cats that have drunk the infected, raw milk.

“It’s weird, actually, how consistently that seems to be happening everywhere,” he said. “It’s pretty sad and shocking. But that’s one of the first things that people see sometimes.”

There is also some suggestion that some cows that have recovered from the virus have been reinfected, although this has not been confirmed.

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“We don’t have any data to support this yet, but there have been anecdotal reports of reinfections in herds,” said Kay Russo, a dairy-poultry vet with RSM Consulting, an international consulting firm.

She said it could just be a persistent infection that is being observed, but also speculated that the virus could be mutating rapidly — and evolving “enough to reinfect an animal.”

And Jason Lombard, one of the speakers at the dairy webinar, said in an email that he had been told by veterinarians that they are observing clinical signs of disease in animals that had been infected, “but I don’t believe any of them have been confirmed via testing.”

As of Oct. 4, California officials have reported 56 infected herds. Although state officials will not disclose the location of these herds, the Valley Veterinarians Inc. website — a veterinary clinic run by large-animal vets in the Central Valley — said the infections are in Tulare and Fresno counties.

Steve Lyle, a California Department of Food and Agriculture spokesman, would not confirm the counties.

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There are more than 200 herds in Tulare County and more than 100 in Fresno County. The state’s largest raw milk dairy is also in Fresno County.

Requests by The Times to observe infected farms or speak with the owners of infected dairies went unanswered by the state and declined by industry insiders.

“We are not recommending farmers engage on this due to farm security issues we’ve had,” said Anja Raudabaugh, chief executive officer of Western United Dairies, an industry trade group for California dairy farmers. “It is very unwise to consider viewing a dairy under quarantine … this is just not the time.”

She said her organization doesn’t want anyone “doxing” farmers or increasing traffic at or near a farm, “both of which have happened.”

In the last week, the H5N1 virus has been detected in wastewater samples collected in Turlock, San Francisco, Sunnyvale and Palo Alto.

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State epidemiologist Erica Pan said it was hard to know where the virus is coming from. While Turlock is a dairy center, the hits in the Bay Area cities could potentially be from wild birds, she said, but the source is not known.

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Opinion: The evidence shows women make better doctors. So why do men still dominate medicine?

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Opinion: The evidence shows women make better doctors. So why do men still dominate medicine?

“When will I see the doctor?” Most female doctors have been asked this question many times. It feels like a slight — a failure to recognize the struggle it took to get to where they are, a fight that is far from over once a woman has her medical degree.

Women now make up more than half of medical students but only about 37% of practicing doctors. That is partly because the makeup of the medical workforce lags that of the student body. But it’s also because persistent sexism drives higher attrition among women in medicine.

Even in households headed by a mother and father who both work, the woman is frequently expected to be the primary caretaker. As a result, female physicians often feel forced to work part time, choose lower-paying specialties such as pediatrics or leave the profession altogether.

That’s unfortunate not just for doctors but also for patients. On the whole, female doctors are more empathetic, detail-oriented and likely to follow through than their male counterparts. In other words, they are better doctors.

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Admittedly, that is a generalization, but it’s one worth making. I experienced it firsthand working with female colleagues, and I’m informed by that experience in addressing my own medical needs. I prefer to see female doctors.

It wasn’t always that way. But after seeing a series of male doctors who were not listening to me, in a hurry to get out of the exam room or appearing only mildly interested in figuring out the cause of my problem, I made the switch — and I’m not going back. While I found that male doctors typically decided what my diagnosis was and how to treat it before entering the exam room, female doctors tended to be open-minded about what my medical issues were and — gasp! — listen to my answers to their questions.

But don’t take my word for it. Look at the data.

One recent study found that both female and male patients had lower mortality rates when they were treated by female physicians. Perhaps not surprisingly, the benefits of getting care from women were greater for women than for men.

“What our findings indicate is that female and male physicians practice medicine differently, and these differences have a meaningful impact on patients’ health outcomes,” said Yusuke Tsugawa, a senior author of the study.

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Female doctors seem more likely to discover the root cause of a medical problem, as we are taught to do in medical school, rather than merely treat the symptoms.

“Female physicians spend more time with patients and spend more time engaging in shared medical decision-making,” Dr. Lisa Rotenstein, a co-author of the study, told Medical News Today. “Evidence from the outpatient setting demonstrates that female physicians spend more time on the electronic health record than male counterparts and deliver higher-quality care. In the surgical realm, female physicians spend longer on a surgical procedure and have lower rates of postoperative readmissions. We need to be asking ourselves how to provide the training and incentives so that all doctors can emulate the care provided by female physicians.”

One reason for the discrepancy might be male doctors’ propensity to be more ego-driven. They may revert to “mansplaining” to patients instead of engaging in an equal, cooperative patient-physician relationship. I’ve been guilty of that myself, so I know it when I see it.

What’s blocking women’s advancement in medicine? Old-fashioned sexism in the workplace is the most obvious answer. Female doctors are paid 25% less than their male counterparts on average, according to the 2019 Medscape Physician Compensation Report, earning an estimated $2 million less over a 40-year career.

There is also a power imbalance. Men are more likely to be full professors at medical schools and presidents of professional medical associations. A 2019 survey found that women oncologists were less likely than their male counterparts to attend scientific meetings because of child care and other demands. And anyone in medicine will attest that these conferences provide opportunities to angle for leadership positions.

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Excluding women from leadership deprives young female doctors of role models. While I haven’t seen female doctors being asked to get coffee for their male colleagues (though I have seen women nurses asked to do so, even recently), the unequal distribution of responsibilities is undeniable. Female physicians are often overburdened with menial, uncompensated assignments, secretarial tasks and committee service that does not necessarily lead to promotions, taking precious time away from activities that would be more likely to advance their careers.

These and other factors lead to higher burnout rates among women physicians. A 2022 American Medical Assn. survey found that 57% of female physicians reported suffering at least one symptom of burnout, compared with 47% of men.

“Women physicians are paid less than men, work harder, have less resources, are less likely to be promoted and receive less respect in the workplace,” Roberta Gebhard, a former president of the American Medical Women’s Association, told the Hill. “With all of these barriers to success in the workplace … it’s no wonder that women physicians are more likely to stop practicing than men.”

The patriarchal system is alive and well in medicine, and it isn’t helping our patients. We must address this antiquated disparity. It is incumbent on medical institutions to champion female physicians, not only as rank-and-file doctors but also as leaders of the profession and its organizations. Patients should also examine their own assumptions and challenge the notion that seeing a male doctor will yield better results.

It’s time for doctors to live up to one of the highest ideals of medicine: that all people should be treated equally. That includes female physicians.

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David Weill is a physician, a former director of Stanford’s Center for Advanced Lung Disease, the principal of the Weill Consulting Group and the author, most recently, of “All That Really Matters.”

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