A new generation of anti-obesity medications offers the promise of dramatic weight loss but there is still a long way to go to make them accessible to those who need them.
Obesity is the last major untapped medical condition - one that more than 100 million Americans share - and drug companies have been trying for decades to develop a treatment.
Finally, medications are coming on the market with the promise of reducing weight by 15% to more than 20%, more than has ever been possible with medications and the kind of weight loss rarely seen outside of surgery.
But so far, only the wealthiest and luckiest have been able to access the first of a new class of medications. That drug, Wegovy, sells for $1,349 for four weekly shots per month.
Insurance typically doesn't cover anti-obesity medications, though obesity is associated with 200 diseases, including diabetes, heart disease and some types of cancer. So, patients in the greatest need often can't get Wegovy. And for some of those who can, they are suffering horrendous side effects.
Just ask Elise Davenport.
Davenport, 40, decided to give up her medication one night in late spring, while lying on her bathroom floor sobbing.
She had been dry heaving violently. Even water made her throw up. Food was so nauseating she couldn't imagine eating. "Nothing is worth this," she thought.
Davenport had lost more than a quarter of her body weight in seven months thanks to medication and eating fewer processed foods.
Lying on that bathroom floor, she decided to taper off Wegovy, even if it meant regaining the pounds she'd struggled for a decade to lose. She thinks the drug was just more than her slimmer body could handle and that better monitoring by her weight loss program might have saved her from the horrible nausea and reflux, sleep issues and depression.
"It just got too much for me," she said.
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Wegovy side effects, supply challenges and unfair distribution
In a way, Davenport was lucky. Most people haven't been able to get Wegovy because it's been in short supply for more than a year. Novo Nordisk, which makes the drug, says it will resolve its production issues this month and will relaunch the drug commercially in the first quarter of next year.
Earlier this year, to reduce the number of new patients who started taking Wegovy, Novo Nordisk took the three lowest, ramp-up doses off the market while filling orders for the higher doses, in an effort to target those who were already taking the drug, said Dr. Jason Brett, executive director of medical affairs, via email.
But instead of deterring all new patients, some were started immediately at one of the two highest doses. The ramp-up doses were created to avoid severe side effects.
Davenport was in a medically monitored weight-loss program that diagnosed her as at-risk for diabetes, though her insulin resistance levels were just below the threshold for pre-diabetes. Starting in October 2021, she cut back on processed foods, was prescribed the diabetes drug metformin and ramped up slowly on Wegovy before the shortage really took hold.
She had no issues on the two lowest doses, but problems started as she moved up to the 1 mg dose early in 2022. She had constant nausea, terrible reflux, a sour stomach.
"I was so nauseated, I couldn't imagine eating anything," Davenport said.
Her lifelong sleep struggles got far worse and she stopped taking pleasure in food or anything else. In late spring, after shedding about 50 of her 199 pounds, she found herself on the bathroom floor.
"Because I was losing so much weight between the drug and the program, I think that's what did it to me," Davenport said.
Dr. Fatima Cody Stanford, an obesity medicine specialist at Massachusetts General Hospital, blames most of Wegovy's severe side effects on such over-dosing. In her busy practice, she's found that some people, particularly those over 60, are extremely sensitive to the drugs and may not need the full 2.4 mg dose.
"The side effects, I think, are secondary to people not prescribing them correctly," Stanford said. "You have to listen to the patient."
She makes sure her patients are symptom-free before advancing them to the next dose.
People who are immediately started on 1.7 mg or 2.4 mg, as some have been during the shortage, are "a disaster waiting to happen," Stanford said. "It's like me throwing a hurricane at your body and you're not even prepared for light rain."
Novo Nordisk's Brett agrees that dosage should be ramped up slowly from .25 mg to the maintenance dose of 2.4 mg.
"Titrating the dose strengths up too quickly or starting at any unapproved dose strength may result in increased rates of adverse events," he said. "This is why the dose strength of the medicine should be increased gradually, as directed by a health care provider and in accordance with the package insert."
In clinical trials, 73% of patients treated with full-dose Wegovy and 47% of those receiving a placebo reported gastrointestinal disorders. The most frequently reported reactions were nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea (30% vs. 16%). Just over 4% of those who received Wegovy quit the treatment because of these side effects, compared to less than 1% of those on placebo.
Obesity medicine specialist Dr. Katherine Saunders said her patients typically do well on Wegovy but that it and other medications should be "part of a comprehensive, individualized and long-term approach."
"We tailor our treatment strategy and we recommend adjustments to diet and behavior in order to minimize side effects," said Saunders, an assistant attending physician at NewYork-Presbyterian Hospital and co-founder of Intellihealth, a medical obesity treatment platform.
Demand for Wegovy has been unprecedented, said Stanford, who is resentful that celebrities and rich people have been getting access to Wegovy to look better, while her patients in real medical need haven't been able to access the drug.
"I should not be getting this to look cuter in my bathing suit. That is not the goal," she said. "I'm really frustrated with the celebrity group taking medications from people I think actually need the medications. I think it's not right."
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Not everyone will benefit from Wegovy or any anti-obesity medication, Stanford warned.
And she's worried about what will happen when these drugs become more widely available. Doctors are not used to prescribing these medications. "We need to be prepared and change our strategy," she said.
The industry is far more enthusiastic than anxious.
Analysts estimate the weight loss medication field could generate $50 billion annually by 2030, with more than 40% of Americans meeting the definition for having obesity and 70% considered overweight.
"This may be the last 100-million-plus type marketplace left untreated in the United States," said George Hampton, CEO of Currax Pharmaceuticals, which sells the weight-loss medication Contrave. Contrave is a 30-year-old drug that targets hunger and cravings and has been shown to reduce weight as much as 11%.
The list price for Contrave runs $625 a month but since 2019, Currax, a private company based in Brentwood, Tennessee, has been offering the drug to people who are uninsured for $99 monthly, Hampton said.
"We're just burying the cost to make sure the patient can receive the medication if they need it and want it," Hampton said.
But the company can't continue doing that indefinitely.
Today, only 2% to 3% of patients with obesity receive medication, typically because their employer has a "Cadillac insurance plan," Hampton said.
Obesity, defined as a body mass index over 30, has been labeled as a disease since 2013 - meaning it is a medical condition, not the result of laziness or bad habits.
"The vast majority of people suffering from obesity do not have some bad lifestyle that the rest of us don't have," Hampton said. "People who are suffering from obesity don't have to feel shame. They have a disease that needs to be treated chronically."
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Most people will have to stay on anti-obesity medications for life, just as those with high blood pressure or high cholesterol need to continue receiving treatment indefinitely.
Insurers and the federal government will have to figure out how to address obesity without bankrupting themselves, Hampton said.
"The competitor for all of us in this space, whether it's a service or a medication, really is obesity coverage," Hampton said. "We've got to find a way to get patients access to the medications."
More new medications on the horizon
The scientific advance that led to the development of Wegovy is also leading to other medications.
The first, generically called tirzepatide, seems likely to be approved by regulators early next year. The drug from Eli Lilly is the same as is now available for people with diabetes under the brand name Mounjaro.
A study published in June found that tirzepatide could help people lose as much as 21% of their body weight, 50 to 60 pounds in some cases.
Both tirzepatide and semaglutide - the generic name for Wegovy and the diabetes drug Ozempic - mimic a naturally-occurring hormone called glucagon-like peptide-1 or GLP-1. Tirzepatide also includes a second natural hormone.
A third anti-obesity medication, currently called AMG-133, is also under development.
Using genetic research, Amgen discovered that people with less of a naturally occurring hormone called glucose-dependent insulinotropic polypeptide, or GIP, also weighed less, giving "us clues on how to design the drug," said Dr. Saptarsi Haldar, an Amgen vice president of research.
AMG-133 inhibits GIP and activates the same GLP-1 system as both semaglutide and tirzepatide. Because of the way it's made, "stepping on the break with one pathway and stepping on the gas for the other," as Haldar put it, AMG-133 lasts longer in the body.
On Saturday, Amgen reported results for the first human trials that showed a handful of volunteers treated once at the highest dose had lost 14.5% of their body weight 85 days later. The dozen participants given three medium or high doses, each a month apart, maintained most of that weight loss 150 days after the third dose, the company reported at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease in California.
Future trials will help determine the exact dose and timing that works best for weight loss as well as for patients with diabetes, Haldar said. "We're going to endeavor to identify the optimum proposition for patients and providers."
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Reconsidering weight loss
Davenport, who lives in the Houston suburb Kingwood, said she's thought a lot about whether she would consider taking Wegovy again. She had to taper off the drug and still felt nauseous for the five or six weeks while it was leaving her system. But she's mostly back to normal now.
She no longer has to choke down her food and actually gets some pleasure from it again.
Still, Wegovy made it easier for her to feel satisfied eating fruit or nuts as a snack, instead of prepackaged junk food, Davenport said.
She's regained about 6 pounds, but processed food has snuck back into her diet, she admits. "I do miss having that drug so I can be like, 'nope, I just want a peach right now.'"
Seeing the impact the drug had convinced her that an inability to lose weight isn't a moral failing, Davenport said.
"It was literally something in my gut being out of balance that was ramping up these cravings for these horrible foods and once I had a drug that corrected that, it suddenly became very easy to exercise and eat right like I had always been told," she said.
That made her think of a co-worker of her sister's who hasn't been able to access medication despite having a very high body mass index.
"It's a really frustrating thing that we blame people for this but then we offer them no sort of treatment or help for it."
Contact Karen Weintraub at email@example.com.
Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.
This article originally appeared on USA TODAY: Wegovy, Mounjaro and weight loss drugs: A look at 2023 availability