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Even stronger obesity drug could further upend weight-loss care

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Even stronger obesity drug could further upend weight-loss care

As a growing number of overweight Americans clamor for Ozempic and Wegovy — drugs touted by celebrities and on TikTok to pare pounds — an even more powerful obesity medicine is poised to upend treatment.

Tirzepatide, an Eli Lilly and Co. drug approved to treat Type 2 diabetes under the brand name Mounjaro, helped people with the disease who were overweight or had obesity lose up to 16% of their body weight, or more than 34 pounds, over nearly 17 months, the company said on Thursday.

The late-stage study of the drug for weight loss adds to earlier evidence that similar participants without diabetes lost up to 22% of their body weight over that period with weekly injections of the drug. For a typical patient on the highest dose, that meant shedding more than 50 pounds.

Having diabetes makes it notoriously difficult to lose weight, said Dr. Nadia Ahmad, Lilly’s medical director of obesity clinical development, which means the recent results are especially significant. “We have not seen this degree of weight reduction,” she said.

Based on the new results, which have not yet been published in full, company officials said they will finalize an application to the U.S. Food and Drug Administration for fast-track approval to sell tirzepatide for chronic weight management. A decision could come later this year. A company spokeswoman would not confirm whether the drug would be marketed for weight loss in the U.S. under a different brand name.

Game changer for obesity treatment

If approved for weight loss, tirzepatide could become the most effective drug to date in an arsenal of medications that are transforming the treatment of obesity, which affects more than 4 in 10 American adults and is linked to dozens of diseases that can lead to disability or death.

“If everybody who had obesity in this country lost 20% of their body weight, we would be taking patients off all of these medications for reflux, for diabetes, for hypertension,” said Dr. Caroline Apovian, a director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital. “We would not be sending patients for stent replacement.”

Industry analysts predict that tirzepatide could become one of the top-selling drugs ever, with annual sales topping $50 billion. It is expected to outpace Novo Nordisk’s Ozempic — a diabetes drug used so commonly to shed pounds that comedian Jimmy Kimmel joked about it at the Oscars — and Wegovy, a version of the drug also known as semaglutide approved for weight loss in 2021. Together, those drugs made nearly $10 billion in 2022, with prescriptions continuing to soar, company reports show.


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In separate trials, tirzepatide has resulted in greater weight loss than semaglutide, whose users shed about 15% of their body weight over 16 months. A head-to-head trial comparing the two drugs is planned.

Mounjaro was first approved to treat diabetes last year. Since then, thousands of patients have obtained the drug from doctors and telehealth providers who prescribed it “off-label” to help them slim down.

Drug suppresses appetite

In California, Matthew Barlow, a 48-year-old health technology executive, said he has lost more than 100 pounds since November by using Mounjaro and changing his diet.

“Psychologically, you don’t want to eat,” said Barlow. “Now I can eat two bites of a dessert and be satisfied.”

Rather than relying solely on diet, exercise and willpower to reduce weight, tirzepatide and other new drugs target the digestive and chemical pathways that underlie obesity, suppressing appetite and blunting cravings for food.

“They have entirely changed the landscape,” said Dr. Amy Rothberg, a University of Michigan endocrinologist who directs a virtual weight loss and diabetes program.

Research has shown that with diet and exercise alone, about a third of people will lose 5% or more of their body weight, said Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine. In the latest tirzepatide trial, more than 86% of patients using the highest dose of the drug lost at least 5% of their body weight. More than half on that dose lost at least 15%, the company said.

The obesity medications help overcome a biological mechanism that kicks in when people diet, triggering a coordinated effort by the body to prevent weight loss.

Potentially serious side effects

“That is a real physical phenomenon,” Aronne said. “There are a number of hormones that respond to reduced calorie intake.”

Ozempic and Wegovy are two versions of semaglutide. That drug mimics a key gut hormone, known as GLP-1, that is activated after people eat, boosting the release of insulin and slowing release of sugar from the liver. It delays digestion and reduces appetite, making people feel full longer.

Tirzepatide is the first drug that uses the action of two hormones, GLP-1 and GIP, for greater effects. It also targets the chemical signals sent from the gut to the brain, curbing cravings and thoughts of food.

Though the drugs appear safe, they can cause side effects, some serious. Most common reactions include diarrhea, nausea, vomiting, constipation and stomach pain. Some users have developed pancreatitis or inflammation of the pancreas, others have had gallbladder problems. Mounjaro’s product description warns that it could cause thyroid tumors, including cancer.


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There are other downsides: Versions of semaglutide have been on the market for several years, but the long-term effects of taking drugs that override human metabolism are not yet clear. Early evidence suggests that when people stop taking the medications, they gain the weight back.

Plus, the medications are expensive — and in recent months, hard to get because of intermittent shortages. Wegovy is priced at about $1,300 a month. Mounjaro used for diabetes starts at about $1,000 per month.

Apovian said that only about 20% to 30% of patients with private insurance in her practice find the medications are covered. Some insurers who previously paid for the drugs are enacting new rules, requiring six months of documented lifestyle changes or a certain amount of weight loss for continued coverage. Medicare is largely prohibited from paying for weight-loss drugs, though there have been efforts by drugmakers and advocates for Congress to change that.

Chronic disease, not character flaw

Still, experts say that the striking effects of tirzepatide — along with Ozempic, Wegovy and other drugs — underscore that losing weight is not merely a matter of willpower. Like high blood pressure, which affects about half of U.S. adults and is managed with medication, obesity should be viewed as a chronic disease, not a character flaw, Aronne emphasized.

It remains to be seen what effect new drug treatments will have on pervasive bias against people with obesity, said Rebecca Puhl, a professor in the Rudd Center for Food Policy and Health, who studies weight stigma. U.S. culture has “deep-rooted beliefs about body weight and physical appearance” that are hard to change, she said.

“Weight stigma could persist or worsen if taking medication is equated with ‘taking the easy way out’ or ‘not trying hard enough,'” she said.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. 

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