CNN Exclusive: Older weight loss drugs are making a comeback as Zepbound, Wegovy remain out of reach for many

By Meg Tirrell, CNN

(CNN) — For Christy Nguyen, menopause hit just as the Covid-19 pandemic did. With both, she said, came unwanted weight gain.

“I had gained 30 pounds in about two years, and so I was sort of desperate to find something” to help with weight loss, the 56-year-old mother of two said. She’d tried WeightWatchers and the keto diet, hoping to lose weight and be able to stop taking her recently prescribed medicines for high blood pressure and cholesterol. But nothing seemed to work.

That’s how Nguyen found herself on a 15-month journey through a new class of medications like Ozempic and Wegovy. Known as GLP-1 receptor agonists, they’re exploding in popularity but can sometimes be impossible to get because of insurance hurdles and shortages. Like an increasing number of patients, Nguyen began taking a decades-old prescription drug for weight loss instead.

“People come in the door seeking treatment with a GLP-1, and then for whatever reason, they can’t get it or change their mind,” said Nguyen’s physician, Dr. Jody Dushay of Beth Israel Deaconess Medical Center.

Older weight-loss medicines have several benefits, Dushay said. They can be more affordable, even out-of-pocket; are less likely to be in shortage; come with different side effects than Wegovy and similar drugs; and are pills instead of injections.

As overall prescriptions of weight-loss drugs have soared, those for older medicines in the category have as well – although on a more modest scale than drugs like Wegovy, according to data from Epic Research provided exclusively to CNN.

Battling insurance and shortages

It started for Nguyen in spring 2022, when a previous doctor prescribed Wegovy. But even though she qualified based on her body mass index – about 35, she said – the medicine costs more than $1,000 a month, and Nguyen’s insurance wouldn’t cover it. So her doctor prescribed its sister drug, Ozempic, which is approved for type 2 diabetes and uses the same key ingredient, semaglutide, at generally lower doses. It’s often used off-label for weight loss.

Nguyen, who lives outside Boston, said she was able to find a three-month supply of Ozempic for $900 through a website that allowed her to order the drug from Canada. Over those three months, she said, she lost 10 pounds.

“It wasn’t crazy fast,” Nguyen said. “It was enough to sort of feel like ‘oh, great. I found something that works.’”

But after three months, Nguyen said, it wasn’t sustainable for her to keep paying so much out of pocket for the medicine. By that point, a new option had come on the market: Mounjaro, a drug similar to Ozempic that’s approved for type 2 diabetes. The manufacturer, Eli Lilly, offered a coupon to lower some patients’ copays, and that helped Nguyen get that medicine for about a year.

She lost an additional 10 pounds and thinks she could have lost even more, except the drug was starting to be in short supply in higher doses, so she was stuck on a lower dose for longer than she otherwise might have been.

Even so, Nguyen said, she’d finally found something that was working for her, something that quieted the “food noise” that had made it hard to lose weight in the past.

“I just kind of felt neutral about it for the first time,” Nguyen said. And more than that, she said, having new medicines like these was gratifying in how she felt the field of medicine was approaching weight loss.

“Suddenly, you sort of feel seen and heard for the first time,” Nguyen said, “when obesity is kind of talked about as a disease rather than as a sort of lazy lifestyle.”

Then the Mounjaro coupon program ended, and Nguyen was left without access to the medicines yet again.

‘I’m not fat enough’

Nguyen’s doctor then tried prescribing an older medicine from the same GLP-1 class, called Saxenda. Nguyen’s insurance denied it, she recalled, “because my BMI was not in the morbidly obese category.”

The US Centers for Disease Control and Prevention defines obesity as a BMI of 30 or more, and Saxenda – as well as other GLP-1 drugs – is approved for people with a BMI of at least 30, or with a BMI of 27 and at least one weight-related condition, like high blood pressure.

The CDC classifies BMI of 35 to 40 as “class 2 obesity” and 40 and higher as “class 3,” or what some refer to as severe or, previously, “morbid” obesity.

“So I’m like, ‘Well, you know, if you want me to become morbidly obese, I guess I’ll come back and talk to you in about a year, because we’ll probably be there by then,’” Nguyen said. “I’m not fat enough, or something.”

In the three months after Nguyen stopped Mounjaro, from August to November, she said, she gained back about 80% of the 20 pounds she’d lost over the previous 15 months.

“It was alarming, the rate I gained it back,” Nguyen said. “It was at least a pound a week.”

That’s when she was referred to Dushay, an endocrinologist focused on obesity and type 2 diabetes at Beth Israel and an assistant professor of medicine at Harvard Medical School. The two started brainstorming about options.

It’s a conversation Dushay says she has with many of her patients as the popularity of new drugs like Ozempic leads people to seek weight loss treatment where they might not have before, but then they encounter barriers to actually getting the medicines.

“I think there is this underlying sense of ‘I should be able to do this on my own,’ which doesn’t apply to a lot of other chronic diseases and which, I think, is a misperception for many reasons,” Dushay said.

The boom in popularity of new drugs, she said, “I think maybe has allowed people to seek medical care for the treatment of a disease the same way you would if you had diabetes or if you had high blood pressure.”

Because of chronic shortages of Mounjaro, Ozempic and Wegovy, insurance denials and myriad other reasons, Dushay and other doctors have been reaching for tools they used before those drugs became available: older prescription medicines used both on- and off-label for weight loss, like phentermine, metformin and bupropion.

For Nguyen, Dushay prescribed bupropion, first approved by the US Food and Drug Administration in 1985 and best known as the brand-name antidepressant Wellbutrin. It’s also approved for smoking cessation and, in 2014, was approved by the FDA for weight loss in combination with another drug, naltrexone, as Contrave.

“You can try it for people in whom afternoon or evening snacking is a big problem or who have lots of craving for sweets,” Dushay said. “Similar to the way that it helps to work for smoking cessation, through cravings – I think that’s the primary mechanism through which it can help.”

Nguyen said in November that after a week on bupropion, she felt it may finally have stopped the continuous weight gain she’d been experiencing since she lost access to Mounjaro.

Older weight-loss drug prescriptions rise

Rates of weight-loss prescriptions among adults characterized as overweight have more than doubled since 2017, according to data from Epic Research based on analysis of millions of electronic health records. Just from 2022 to 2023, the data shows, rates jumped 25%.

The biggest increases are for semaglutide and tirzepatide, the generic names for Ozempic and Wegovy (semaglutide) and Mounjaro and Zepbound (tirzepatide). But there have also been significant increases in prescription rates of older medicines.

The prescription rate for bupropion rose 29% between 2017 and 2023, according to Epic’s data, while the rate for phentermine, approved by the FDA in 1959, is up 34%. The analysis looked at adults characterized as overweight who had prescriptions for any medicines in a given year and the rates who were prescribed a weight-loss drug.

The numbers are bigger for the newer medicines: Semaglutide’s prescription rate nearly doubled in the past year alone, while tirzepatide’s rose 141%. Semaglutide was approved as Ozempic for type 2 diabetes in 2017 and cleared for chronic weight management as Wegovy in 2021. Tirzepatide, as Mounjaro for type 2 diabetes, was cleared in May 2022 and last month for weight loss as Zepbound.

“Not everybody has insurance coverage for the new medications,” said Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine who uses older medicines, as well as newer ones, extensively in his practice. “So they’re doing what they can to lose weight.”

The older medicines can be very effective, he said, but as with any class of medication, it’s a matter of finding the right one for each person. Phentermine, for example, can increase heart rate and blood pressure, so he said he wouldn’t reach for that drug for someone with cardiovascular disease.

Phentermine was part of the notorious fen-phen combination that led to serious heart valve problems in some patients; the other medicine in the combination, fenfluramine, was pulled from the market in 1997. The FDA didn’t request removal of phentermine.

The medicine was also approved as part of a combination with another drug, topiramate, as the weight-loss drug Qsymia in 2012.

Clinical trials of Qsymia and Contrave didn’t yield as much weight loss as the GLP-1 class, and the medicines never became commercial successes.

For some people, the newer medicines are less appealing precisely because they are new. Sixty-two-year-old Henry Benson said he’d lost about 70 pounds over four years through a lifestyle program with Dushay and was hoping to lose 20 more. He and Dushay discussed Wegovy and other similar medicines, and he decided they weren’t for him.

The potential side effects associated with GLP-1s sounded “particularly unpleasant,” he said; they can include nausea, vomiting and constipation, particularly as patients first start the medicines.

Additionally, he said, “the drug is relatively new, so we don’t really know what the long-term side effects are. … I just I looked at all of that and I said, ‘You know what, I just don’t think that this is right for me.’”

He and Dushay settled on metformin, a generic drug approved in 1994 for type 2 diabetes. He’s lost about five more pounds, and his goal is to stop taking the medicine after losing about 15 additional pounds and then to maintain his weight loss without medication. He noted that he’s already been able to stop other medicines, like statins, because his cholesterol levels fell with changes he made in the kinds of foods he was eating.

And although physicians are happy to have new tools like GLP-1s, their increased use can come with downsides, said Dr. Zhaoping Li, a professor of medicine and chief of the Division of Clinical Nutrition at the University of California, Los Angeles.

“People are losing weight, all right, but they’re also losing a lot of muscle,” which can be particularly worrisome for geriatric patients, Li said. “Another major issue is, people are eating so little, they start to have malnutrition and vitamin deficiencies. So it’s not a free ride for everyone to a better place.”

Those risks, doctors said, must be balanced with dramatic benefits from the new medicines; Dushay and Aronne both cite trial results from this year showing that Wegovy can reduce the risk of heart attacks, strokes or heart-related death in people with cardiovascular disease by 20%, in addition to weight loss.

And with Zepbound newly available from Eli Lilly, patients like Nguyen are hoping for better luck getting access to it. Dushay said that about 75% of her requests for insurance coverage of the drug, which was priced at a discount to Wegovy but still at more than $1,000 per month, have been getting denied. Wegovy, Dushay said, has improved coverage after being on the market for longer, but it’s in shortage, particularly in lower doses.

Like it did for Mounjaro, Lilly is offering a coupon to lower some patients’ out-of-pocket costs. Nguyen said her insurance denied coverage, but the savings card allows her to pay $550 a month. She plans to use that as she starts on lower doses of Zepbound and, when she’s reached a higher dose, potentially switch to Wegovy, which is covered.

She took her first injection of Zepbound last week.

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