Letha Walton suffered from rheumatoid arthritis for years. “It was awful,” said Walton, 57, of Wenatchee, Wash. “It just got worse and worse.”
She had high blood pressure and was obese. Doctors advised her to diet and exercise, which she did, but to no avail.
She then found a doctor who prescribed Wegobi, a new obesity drug, and says she has not only lost more than 50 pounds, but also cured her arthritis and is no longer taking blood pressure medication.
Her new doctor, Dr. Steffie Dees, an internist and obesity medicine specialist in private practice in Seattle, said Walton represents a growing movement in obesity medicine.
Proponents call this “obesity first”: the idea is to treat obesity with drugs approved for that purpose. When obesity is controlled, they point out, a patient's other chronic diseases tend to improve or disappear.
“We're treating the medical condition of obesity and the associated comorbidities at the same time,” Dr. Dees said.
Some are wary: Obese people can be irritated when their doctor talks about their weight. And it's true that new obesity drugs may have unexpected benefits beyond obesity, such as reducing inflammation. But the drugs are expensive, and many of their other potential benefits have yet to be substantiated in rigorous studies.
Dr. Gordon Guyatt, a clinical trials expert at McMaster University in Ontario, said a sensible approach would be to use drugs — often cheap generics — that have been thoroughly tested and proven to be effective in treating conditions that often accompany obesity, such as high blood pressure, high cholesterol, arthritis and sleep apnea.
He said obesity medications are meant to treat obesity.
But many doctors, like Dr. Dees, are shocked by stories like Walton's and say they see them all the time in their practice. They argue there is reason to believe the drugs' effectiveness for other medical problems is independent of weight loss.
The idea of treating obesity first is a change from traditional medical practice: When patients come to the doctor complaining of obesity and related chronic conditions such as high blood pressure, high blood sugar or sleep apnea, many doctors prescribe drugs for each of those conditions. They might also recommend exercise or dietary changes, but there is often no clear guidance, and decades of research have repeatedly shown that most people never actually lose weight.
By combining diet and exercise with powerful new drugs like Novo Nordisk's Wegovy and Eli Lilly's Zepbound, doctors hope to treat obesity with just one medication while also improving related symptoms.
“Losing weight can also treat high blood pressure, fatty liver, diabetes, high cholesterol and high triglycerides,” says Dr. Caroline M. Apovian, an obesity medicine specialist at Brigham and Women's Hospital in Boston.
Dr Apovian, who advises companies that make obesity treatments, says patients are ecstatic to be able to take one pill instead of many and, of course, to lose weight after years of trying to diet in vain.
Experts point to another benefit: Patients tend to stay on their obesity medications, but many people who take essential health medications like statins stop taking them.
Still, there are few rigorous studies showing that treatment reverses obesity-related conditions, and large-scale clinical trials that randomly assign patients to obesity drugs or a placebo are needed to establish whether a drug can have the desired effect on multiple conditions.
Maybe not.
The history of medicine is replete with examples of treatments that everyone thought would work, until clinical trials showed they didn't.
Experts widely expected that menopausal hormones would prevent heart disease, so much so that Wyeth, maker of the then-popular Prempro, asked the Food and Drug Administration to include a heart disease prevention claim on the drug's label. But when the National Institutes of Health conducted a large-scale, rigorous study, the Women's Health Initiative, researchers had to end clinical trials early for safety reasons because women taking the drug had an increased risk of heart disease, blood clots, stroke, and breast cancer.
Additionally, a federal study looked at whether a widely used antioxidant supplement, beta-carotene, could reduce the risk of cancer and heart disease. The supplement had no effect and slightly increased the risk of lung cancer in people who smoked or were exposed to asbestos.
Two federal studies looked at whether a high-fiber diet reduces the risk of colon cancer, and researchers were surprised to find no evidence that it did.
But there's reason to think that the new obesity drugs might be different: They seem to have effects on the brain and body that go beyond suppressing appetite.
The benefits could be almost immediate, said Dr. Susan Z. Yanofsky, co-director of the Obesity Laboratory at the National Institute of Diabetes and Digestive and Kidney Diseases, who noted that Novo Nordisk's clinical trials of Wegovy in heart disease patients showed a reduction in cardiac complications early in treatment, before patients lost significant weight.
The company now reports that kidney function also improved, independent of weight loss: Participants who took Wegovy and lost little weight saw the same degree of improvement in kidney function as those who lost a lot of weight.
Novo Nordisk recently tested Ozempic in patients with diabetes and kidney disease and found the same results: Kidney function was better preserved in the group taking Ozempic, regardless of weight loss. Dr. Florian MM Valles, the company's corporate vice president of global medical affairs, noted that participants' initial weight also didn't matter. “Whether you had a BMI over 30 or under 30, the impact on the primary outcome was the same,” he said.
Dr. Daniel Drucker, an obesity researcher at the Lunenfeld Tannenbaum Institute at Mount Sinai Hospital in Toronto, said much of the benefit may be due to the drug's ability to reduce inflammation, which occurs before any weight loss occurs.
Dr. Drucker, who has worked on drug discoveries and consults for companies that manufacture new drugs, was surprised by the reaction from patients after a paper he co-authored showing that the obesity drug tirzepatide (Zepbound) could reduce inflammation in mice was covered in the media.
It's not just mice, patients told Drucker in an email. A woman who had suffered from rheumatoid arthritis for years sent Drucker photos of her hands before and after she started ZepBound to treat obesity. In the photos before ZepBound, her hands were swollen and painful, despite her being on arthritis medication. But in the photos after ZepBound, the swelling and pain had disappeared.
“Within a few days, all the pain in my joints was gone,” the woman said in a phone interview, asking not to be named out of concern that future employers would notice her illness.
Eli Lilly and Novo Nordisk, the makers of Zepbound and Wegobee, are testing variations of the drugs in hopes of making them even more effective at reducing weight.
In addition to the results so far in heart patients, Novo Nordisk has found in a separate clinical trial that Wegovy improves physical function, such as exercise capacity, in patients with diabetes and heart failure. Eli Lilly has found that Zepbound helps treat sleep apnea. Other clinical trials currently underway are testing obesity drugs as treatments for depression, addiction, schizophrenia, Parkinson's disease and Alzheimer's disease. A number of other companies are working on developing new obesity drugs that could also be used for other conditions.
“This is the way clinical research for new drugs should be done,” said Dr. Ezekiel Emanuel, co-director of the Institute for Healthcare Transformation at the University of Pennsylvania.
But determining which drugs work for which conditions takes a long time — clinical trials can take years and cost millions of dollars — and many doctors may not want to wait.
“I'm very sympathetic to clinicians who say, 'Let's try this approach while researchers gather more data,'” Emanuel said, adding that in oncology, once a drug is approved, it's common for doctors to use it for other conditions at their discretion.
Moreover, when it comes to the obesity drugs, off-label trials (a small recent study showed that one of the drugs may slow the progression of Parkinson's disease) have shown “what a miracle drug combination these are” and that the effects were “totally unexpected,” he added.
Others, including representatives from companies such as Eli Lilly and Novo Nordisk, have cautioned against “obesity first” and said it would be wise to wait for the results of clinical trials.
Dr. Scott Hagan, a primary care physician in Seattle, goes a step further and takes an “obesity last” approach.
When a patient comes in with obesity and obesity-related symptoms, doctors will first treat the associated symptoms with medications that are known to work, and then only consider trying obesity medications if the patient is comfortable with them and their other symptoms don't improve, Dr. Hagan said.
Obese people tend to have long, strained relationships with doctors who blame them for their weight, despite trying to diet and exercise for years, sometimes decades, he added. He said that when obesity is the first thing doctors try to treat, many give up.
“My priority is building trust in relationships,” he said.
