Lesa Walton suffered from rheumatoid arthritis for years. “It was awful,” said Ms. Walton, 57, who lives in Wenatchee, Wash. “I kept getting sicker and sicker.”
She also had high blood pressure and was obese. Doctors told her to diet and exercise, which she did, to no avail.
Then he found a doctor who prescribed Wegovy, one of the new obesity drugs. Not only did he lose more than 50 pounds, he said. her arthritis cleared up and she no longer needed pills to lower her blood pressure.
Her new doctor, Dr. Stefie Deeds, an internist and obesity medicine specialist in private practice in Seattle, said Ms. Walton exemplifies a growing movement in obesity medicine.
Advocates call it “obesity first.” The idea is to treat obesity with drugs approved for this use. As obesity is brought under control, they note, the patient’s other chronic diseases tend to improve or go away.
“We are treating the medical condition of obesity and its associated complications at the same time,” said Dr. Dinches.
Others are wary. People with obesity can be put off when a doctor reports their weight. And, yes, new obesity drugs may have unexpected benefits beyond obesity, such as reducing inflammation. But the drugs are expensive, and many of the other potential benefits have not been proven in rigorous studies.
Dr. Gordon Guyatt, a clinical trials expert at McMaster University in Ontario, said the prudent approach is to use drugs — often inexpensive generics — that have been well-tested and proven to treat conditions that often accompany obesity, such as high blood pressure, high cholesterol, arthritis and sleep apnea.
Obesity drugs, he said, are for treating obesity.
However, many doctors, such as Dr. Deeds, are impressed by stories like Ms. Walton’s, which they say they see often in their practices. There is reason to believe that the drugs’ effects on medical problems other than obesity may be independent of weight loss, they argue.
The idea of treating obesity first is a change from standard medical practice. When patients come in with obesity and other related chronic conditions, such as high blood pressure, high blood sugar, and sleep apnea, many doctors prescribe medications for each condition. They can also advise exercise and dietary changes — but often without any clear guidance and, as decades of studies have repeatedly shown, without any real prospect that most people will lose weight.
By starting with a powerful new obesity drug, such as Wegovy from Novo Nordisk or Zepbound from Eli Lilly, in addition to diet and exercise, doctors hope that while treating obesity using just one drug, associated conditions they will improve.
As says Dr. Caroline M. Apovian, an obesity specialist at Brigham and Women’s Hospital in Boston, “You get the weight loss and you’ve got high blood pressure, fatty liver, diabetes, high cholesterol. , high triglycerides.”
Dr. Apovian, who has advised obesity drug companies, says patients are excited to take one drug instead of several and, of course, lose weight after years of fruitless dieting.
Experts also describe another advantage: patients often continue to take their obesity drugs, while many who take drugs they need to be healthy, such as statins, stop taking them.
However, there are still few examples of rigorous studies showing that the medical conditions that accompany obesity go away when it is treated. Large clinical trials that randomly assign patients to obesity treatment or a placebo are needed to see if the drug has the hoped-for effect in multiple conditions.
Maybe not.
Medical history is littered with examples of treatments that everyone thought would work until a clinical trial showed they didn’t.
Experts widely expected menopausal hormones to prevent heart disease, and Wyeth, the maker at the time of the wildly popular Prempro, even asked the Food and Drug Administration to put heart disease protection on the drug’s label. But when the National Institutes of Health conducted a large and rigorous study, the Women’s Health Initiative, researchers had to end the clinical trial early for safety reasons: Women taking the drug had an increased risk of heart disease, blood clots, strokes episodes and breast. Cancer.
Then there was the federal study asking whether beta carotene, a widely used antioxidant supplement, could reduce the risk of cancer and heart disease. The supplement did not, and it slightly increased the risk of lung cancer among smokers and those exposed to asbestos.
Two federal studies looked at whether a high-fiber diet reduced the risk of colon cancer. The researchers were surprised to find no such evidence.
However, there is reason to believe that new obesity drugs could be different. They appear to have effects on the brain and body that go far beyond suppressing urges to eat.
These effects can be seen almost immediately, said Dr. Susan Z. Janowski, co-director of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases. He noted that when Novo Nordisk conducted a clinical trial of Wegovy in people with heart disease, heart complications were reduced early during treatment, before the patients lost a lot of weight.
The company now reports that they also had improvements in their kidney function, independent of weight loss. Participants taking Wegovy who lost very little weight had the same improvements in kidney function as those who lost a lot.
A recent study by Novo Nordisk that tested Ozempic in people with diabetes and kidney disease found the same thing: kidney function was better preserved in the Ozempic group, an effect that was independent of weight loss. Dr. Florian MM Baeres, the company’s corporate vice president of global medical affairs, noted that participants’ initial weight also did not matter. The effect on the primary outcome was the same, he said, “whether you start at a BMI above 30 or below 30.”
A large part of the effect may be the drugs’ ability to reduce inflammation, said Dr. Daniel Drucker, an obesity researcher at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital in Toronto. Appears before weight loss.
Dr. Drucker, who helped discover the new drugs and consults with the companies that make them, was surprised by the response from patients after the media reported on a paper he authored showing that the obesity drug tirzepatide, or Zepbound, can reduce inflammation. In mice.
Not just in mice, the patients told him in an email. A woman who suffered from rheumatoid arthritis for years sent Dr. Drucker photos of her hands before and almost immediately after starting Zepbound for obesity. In the previous photo, her hands were swollen and painful, despite the arthritis medication she was taking. In the after photo, the swelling and pain were gone.
“Within a few days, all the pain in my joints was gone,” the woman said in a phone interview. she requested anonymity out of concern that future employers might become aware of her illness.
Eli Lilly and Novo Nordisk, the makers of Zepbound and Wegovy, are testing variations of the drugs in the hope that they will be even better at inducing weight loss.
So far, in addition to the results in people with heart disease, Novo Nordisk found in another clinical trial that Wegovy improved physical function – such as the ability to exercise – in people with diabetes and heart failure. Eli Lilly found that Zepbound can help with sleep apnea. Other trials underway are testing obesity drugs as treatments for depression, addiction, schizophrenia, Parkinson’s disease and Alzheimer’s disease. Dozens of other companies are working on new obesity drugs that may apply to other conditions.
“This is the way clinical research for new drugs should be done,” said Dr. Ezekiel Emanuel, co-director of the Institute for Health Transformation at the University of Pennsylvania.
But evaluating which drugs effectively treat which conditions will take a long time. Clinical trials take years and cost millions of dollars. Many doctors may be reluctant to wait.
“I’m very sympathetic to clinicians who say, ‘As researchers get more data, we’ll try this approach,'” said Dr. Emmanuel. It’s common in oncology, he added, that once a drug is approved, doctors can use it for other diseases at their discretion.
With obesity drugs, he added, off-label experimentation — such as a recent small study showing that one of the drugs can slow the progression of Parkinson’s disease — shows “what a miracle set of drugs these are,” with results that were “totally unexpected.”
Others caution against “obesity first,” including representatives of companies such as Eli Lilly and Novo Nordisk, saying it’s wise to wait for results from clinical trials.
Dr. Scott Hagan, a Seattle primary care physician, goes further, moving toward a “last obesity” approach.
If a patient comes in with obesity and obesity-related conditions, he starts by treating the related conditions with drugs he knows can work. Only later, when patients feel comfortable with it and if other conditions don’t improve, will he discuss trying obesity drugs, Dr. Hagan said.
People with obesity, he added, tend to have a long history of rocky relationships with doctors who blame them for their weight, despite having spent years, even decades, trying diets and exercise. Many of them, he says, will be put off if the first thing he tries to tackle is their obesity.
“My priority,” he said, “is establishing trust in a relationship.”
