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Weight-loss drugs like Ozempic, Mounjaro, Wegovy gain popularity, effectiveness


Rachel Graham has battled excess weight for years, cycling through trendy diets, various drugs, even bariatric surgery. Nothing worked for long. But last summer, she started a new medication, and today is 40 pounds lighter — and still shedding weight.

“It used to be that if I saw food, I would want to eat it,” said the 54-year-old Graham, who is 5-foot-7 and 190 pounds. “Now, if I have three or four bites of food, I don’t want to eat more.”

The drug she’s taking, Mounjaro by Eli Lilly, is part of a new crop of therapies that experts are hailing as a medical milestone — a long-sought way to transform the treatment of obesity, one of the nation’s most serious health threats.

Designed for diabetes but used for obesity at higher doses, the medications induce loss of 15 to 22 percent of body weight on average — more than enough to significantly reduce cardiovascular and other health risks. That makes them far superior to old-style diet pills that delivered smaller benefits along with nasty side effects such as high blood pressure and loose stools.

But during the past year, soaring demand for the drugs has ignited a mad scramble, exposing some of the most persistent problems in the nation’s health-care system, including supply shortages, high costs and health-care inequities.

Tensions are surging as patients with diabetes and those with weight problems sometimes compete for the same medications, which are self-administered in weekly injections. Some doctors worry that the drugs, which might have to be taken for life, will overshadow the need for lifestyle changes involving diet and exercise.

Zhaoping Li, a professor of medicine and chief of the division of clinical nutrition at the University of California at Los Angeles, said the new drugs represent important tools but are not a silver bullet.

“I don’t want people to lose their attention on the fundamental issue — we really need to help each individual have the best lifestyle for their bodies and themselves,” Li said.

Mounjaro, the drug Graham is taking, is approved by the Food and Drug Administration for Type 2 diabetes but not for obesity; that approval may occur next year. In the meantime, many doctors are prescribing the drug “off-label” for weight loss — which is permitted once a treatment is cleared for another use.

Another diabetes drug — Ozempic, made by Novo Nordisk — is in such hot demand for weight loss that many frustrated diabetes patients cannot find the blood sugar-lowering medication. Supplies ran short after Ozempic was touted by celebrities and others on social media as an effective off-label substitute for the company’s obesity treatment, Wegovy. That drug, a high-dose version of Ozempic, went into shortage following production problems.

Diabetes advocates, incensed that some people are using the diabetes drugs to lose a few pounds, say the treatments should be reserved for patients with blood-sugar problems. Recently, Eli Lilly tightened the terms of its coupon that sharply limit out-of-pocket costs for Mounjaro by requiring patients to attest they have diabetes.

But obesity specialists argue that patients with serious weight problems have an urgent need for new medications and that they have fewer treatment options than those with diabetes. More than 40 percent of U.S. adults are obese and another 30 percent are overweight, according to the federal government. At least 200 diseases, including heart conditions, cancer and kidney disease, are linked to obesity.

The competition among vulnerable patients “should not be happening,” said family physician Reshma Ramachandran, a health services researcher at Yale School of Medicine. “Both groups need the medications.”

Graham said she resents suggestions that people with excess weight are “stealing” medications from diabetes patients. She said she was active and athletic most of her life but that back surgery in 2017 made it difficult for her to do vigorous exercise. She said she is trying to avoid ending up like her late father, who lost both legs to diabetes.

“I am prediabetic and have been battling against becoming diabetic for the last six years,” said Graham, who lives near San Diego.

Cost and coverage issues also are affecting access to the new drugs. List prices run from about $1,000 to more than $1,300 a month, and private insurance coverage, while available for diabetes, is inconsistent for weight-loss treatments. Medicare does not cover weight-loss drugs — even though the federal health program for older Americans pays for bariatric surgery.

The high costs appear destined to increase the rampant disparities in weight-loss medicine, in which many drugs and services are available only to those who can pay out of pocket. Ramachandran said her patients of color, many of whom are uninsured, “are not able to even consider these medications,” she said.

The problem is particularly concerning for African American women, who have the highest obesity rates in the nation, obesity specialists said.

“The number one distressing and upsetting issue when it comes to these medications is that the population most in need are unable to afford or have access to it,” said Robert Kushner, an endocrinologist at Northwestern Medicine who led a late-stage clinical trial for Wegovy sponsored by Novo Nordisk.

For almost a decade, the American Medical Association has recognized obesity as a chronic illness. Yet in a country that glorifies thinness, excess weight remains a fraught issue, with many people, including some health-care providers, viewing obesity as the result of poor willpower, a bad diet and inadequate exercise.

“Frequently, a provider will say to a patient, ‘You know, you are too fat, and you need to move more and eat better,’” said obesity expert William Dietz, director of the STOP Obesity Alliance, an advocacy group based at George Washington University. “But there are very few people who have not tried that, and lost weight several times and then regained it.”

Complicating matters is the tumultuous history of weight-loss medications. For years, diet drugs were viewed as vanity treatments or outright quackery, and many were pulled from the market because of dangerous side effects, including death.

After World War II, amphetamines, which suppress appetite but can be addictive, were used widely for weight loss. In the late 1990s, “fen-phen” — a combination of fenfluramine and phentermine — was withdrawn after fenfluramine was linked to heart valve problems. Phentermine is still used. As recently as 2020, a drug called Belviq was voluntarily withdrawn amid concerns that it raised the risks of cancer.

During the last decade, science’s understanding of obesity has deepened, and specialists hope improved treatments and societal attitudes will follow.

“Obesity is a disease,” said Ania M. Jastreboff, an obesity medicine physician and director of Yale’s Weight Management and Obesity Prevention program. “But we should not only say it’s a disease, we should treat it as if it’s a disease.”

She led a trial testing tirzepatide, one of the new medications, for weight loss and has consulted for Lilly, Novo Nordisk and WW (formerly Weight Watchers), among other companies with interests in weight loss.

The new weight-loss medications belong to a class of drugs developed to mimic naturally occurring hormones that increase insulin production and suppresses appetite. The drugs, which include active ingredients such as tirzepatide and another molecule called semaglutide, work on brain receptors that signal satiety, creating a feeling of being full even when patients eat much less than usual, but enough to stay healthy. Semaglutide mimics a hormone called GLP-1, for glucagon-like peptide 1; tirzepatide includes that and another hormone.

The effectiveness of some of the new drugs approaches that of gastric bypass surgery, the gold standard for treating obesity.

The market for the medications could be vast. Analysts at Morgan Stanley recently said obesity drugs are “set to become the next blockbuster pharma category,” estimating global sales could reach more than $50 billion in 2030, up from $2.4 billion currently.

John, a 19-year-old Connecticut college student, used to get winded walking up a flight of stairs. His back hurt, and he was prediabetic. But during the past year, while taking Ozempic, he has dropped 109 pounds, going from 305 to 196.

“It was my key to a new life,” said John, who is 5-foot-8 and spoke on the condition that his last name not be used to protect his privacy. “I have a new mind-set, and my life is completely different.”

Although John does not have diabetes, his insurance, unlike many health plans, is paying for Ozempic “off label” for weight loss.

These days, he walks up four flights of stairs at a Target store near his home “just because I can.” Sometimes, he puts off buying new clothes because he knows he might lose 10 pounds in a matter of weeks, and the clothes will be too big.

When he goes out, he said, “I’m not being stared at, like ‘Oh my God, there’s the 300-pound child.’”

The active ingredient in John’s treatment is semaglutide, which Novo Nordisk developed a decade ago as a once-a-week alternative to another diabetes drug injected daily. The FDA approved Ozempic in 2017 for patients with Type 2 diabetes.

When patients lost substantial weight, the company tested a higher dose in people who didn’t have diabetes. The result, in a key clinical trial, was an average weight loss of about 15 percent. In June 2021, the FDA approved a weekly injection of 2.4 milligrams for chronic weight management, along with a reduced-calorie diet and increased exercise. The drug, sold under the brand name Wegovy, was cleared for individuals with a body mass index of 30 and above, or a BMI of 27 or more and at least one weight-related ailment.

(BMI is a calculation based on height and weight that provides a rough estimate of body fat. People are considered overweight if they have a BMI of 25 to 29 and obese with a BMI of 30 or more, according to the CDC. The measurement has become increasingly controversial, with critics saying it does not accurately represent the health of individuals.)

Within months of being approved, Wegovy was in short supply, because of unexpectedly strong demand and production problems. In a tweet this year, billionaire Elon Musk attributed his weight loss to fasting — “And Wegovy.”

Some physicians who prescribed Wegovy for overweight patients switched them to the diabetes drugs Ozempic or Mounjaro when Wegovy became unavailable. Celebrities and others who were not obese also pursued Ozempic, fueling more than 287 million views of #Ozempic on TikTok.

“When you are in Hollywood and Beverly Hills and something is available that could give you weight loss that is effective, quick and relatively harmless, people are going to do what they are going to do to get the drug, whether they get it from Canada or Mexico or from a doctor who will prescribe it off label,” said Nancy Rahnama, an obesity specialist in Los Angeles.

Rahnama said she would prescribe Ozempic only for patients with elevated blood sugar. She prescribes Wegovy instead of Ozempic for weight loss, if it is available, because the drug is specifically approved for that use.

Novo Nordisk spokeswoman Allison Schneider, in a written response to questions, said the Ozempic shortage reflected “incredible demand coupled with overall global supply constraints.” She said the company is taking steps to ease the shortages.

Regarding Wegovy, Schneider said the company is on track to make all dose strengths … available in December and a broad commercial re-launch is expected to commence next year.”

Clinical trial participants who took tirzepatide, the Lilly compound, lost an average of as much as 22.5 percent of their body weight, or 52 pounds, in 72 weeks or less, according to a study published in the New England Journal of Medicine. Forty percent lost more than that.

The FDA, which approved Mounjaro in May for Type 2 diabetes, is expected to clear the drug for weight loss next year. Lilly said Mounjaro is not in short supply and that the company is monitoring demand “with a focus on access for people with Type 2 diabetes.”

Side effects may include nausea, diarrhea and constipation, but doctors said those problems usually disappear after doses are tailored to each patient.

Price remains an impediment for many patients wanting to use the drugs for weight loss, doctors say. A four-week course of Ozempic has a list price that averages $892; Wegovy’s price tag is about $1,350 a month, while Mounjaro is about $975. The actual cost to patients depends on their insurance or coupons provided by manufacturers and pharmacies.

Robert Gabbay, chief scientific and medical officer for the American Diabetes Association and a practicing endocrinologist, said he recently had a patient “fly in from overseas and … pay out of pocket” for one of the drugs. Other patients have told him they didn’t start taking the medication he prescribed because they could not afford it.

The nonprofit Institute for Clinical and Economic Review, which assesses clinical data to determine what it considers a fair price for drugs, concluded that semaglutide provided a health benefit compared with lifestyle modification alone but that its price would have to be reduced by 44 percent to 57 percent to make it cost effective.

To increase access to the new medications, lawmakers, advocacy groups and drugmakers are pushing legislation to lift a decades-old prohibition on Medicare coverage of weight-loss drugs. The Treat and Reduce Obesity Act has been pending in Congress for years, but backers hope the emergence of highly effective drugs — and estimates showing obesity is costing the nation billions of dollars in medical bills — could provide momentum for passage.

Medicare spending on the drugs is likely to be high, given the large proportion of people who might be eligible.

The bill’s prospects would be improved if a Novo Nordisk study, expected to be completed next year, is successful. That trial is designed to show that semaglutide reduces the risk of heart attacks, stroke and death in overweight and obese patients who have had heart disease — thus proving that medication-assisted weight loss saves lives.

Managers of the federal workforce already have committed to offering weight-loss medications. The Office of Personnel Management, which oversees health-care plans for millions of government workers, clarified this year that insurers “are not allowed to exclude anti-obesity medications from coverage based on a benefit exclusion or a carve out.”

Gary Foster, chief scientific officer for WW, said the new drugs leave plenty of room for traditional weight-loss organizations such as his. WW will continue its focus on the “behavioral” side of weight loss, Foster said, helping people with healthful eating and physical activity — both of which are part of the regimen that accompanies use of the drugs.

“We see treatment advances in this field as good for people who suffer from obesity. We don’t see that as threats. There’s no alarm about this,” Foster said.

A “precision medicine” approach to obesity could further bolster the drugs. Andres Acosta, an assistant professor of medicine and a consultant in gastroenterology and hepatology at Mayo Clinic, said he is trying to perfect a test that uses biomarkers to determine which weight-loss drug will work best for each patient, to move the therapy beyond trial and error.

At Mayo, in Rochester, Minn., this is done with a battery of blood tests. But Acosta also has spun off a company, Phenomix Sciences, that uses genetics to help select the approach that will produce the greatest weight loss in each person. Someday, the company hopes to make the process as easy as swabbing the inside of a patient’s cheek.

“If we can predict who is going to lose more than 10 percent or more than 20 percent, then it will really be worth your time, effort and money,” Acosta said.