The potential cessation of supply for widely-used weight loss medications could result in several individuals losing their ability to obtain them.
"I've tried dieting with WeightWatchers, I've gone keto, and I've consulted a nutritionist," shared a 58-year-old grandmother from Knightdale, North Carolina, outside Raleigh. Some of these methods worked temporarily, but eventually, they failed.
Towards the end of 2022, she weighed around 212 pounds and was concerned about her health following the deaths of her brother and both parents due to heart disease. McCaskill began using Mounjaro, a diabetes drug, off-label for weight loss. This drug belongs to a class called GLP-1 receptor agonists, which includes Ozempic, Wegovy, and Zepbound.
She declared, "It saved my life."
However, the drug was expensive, and after switching to a cheaper version from a compounding pharmacy in 2022, she now fears losing access to her medication due to the FDA's announcement that the brand-name drug shortage has ended, which means compounding must stop.
The Compounding Quality Act of 2013 enabled many people to obtain costly GLP-1 medications at lower prices through compounding pharmacies, despite concerns from some physicians about potential safety issues because these drugs are not FDA-approved. But for individuals like McCaskill, this law proved to be a lifeline. As manufacturers are ramping up supply, their access to these drugs is quickly changing.
"I'm heartbroken, at least," she stated.
Within a year, McCaskill claimed to have lost nearly 100 pounds and maintained her current weight of about 117 pounds. Her blood pressure has lowered, and her A1C, triglycerides, and eating habits have significantly changed for the better. She now exercises more frequently.
Her four granddaughters, aged 6 to nearly 12, served as her main motivation to start the medication. "They cheer me on, and I've never been more active with them," she said.
McCaskill's insurance never covered Mounjaro. Although the drug contains the active ingredient tirzepatide and was FDA-approved in May 2022 for type 2 diabetes, McCaskill did not have diabetes. Most plans do not cover GLP-1 drugs for weight loss purposes.
She paid out-of-pocket for Mounjaro, utilizing a coupon from manufacturer Eli Lilly that reduced the cost by half. However, it still cost around $500 monthly.
When Lilly's coupon program ended in the summer of 2023, her healthcare provider suggested another option: compounded tirzepatide, nonexistent FDA approval but legally available through a local pharmacy. It cost less than $250 for a monthly supply. She continued to benefit from this version and even persuaded her husband to try it.
However, now she's worried about having to discontinue their usage.
No longer in shortage
Last week, the FDA updated its database of drugs in shortage by removing tirzepatide, which had been on the list since 2022 due to extraordinary demand. This means that compounded tirzepatide, such as McCaskill's local pharmacy, can no longer be produced.
Although it suggests that branded tirzepatide-based drugs, such as Mounjaro for diabetes and Zepbound for weight loss, are now widely available, it has thrown people like McCaskill into a state of panic.
"I worked until almost 10 o'clock last night answering patients' questions," said Michele Kessler, a physician assistant at Durham Women's Clinic in North Carolina and McCaskill's provider. "Suddenly, all these patients who are doing well will be forced to stop without warning."
Compounding of medicines that are essentially copies of commercially available drugs is permitted by the FDA during a shortage, but once a shortage is resolved, it's allowed only if it's not done "regularly or in inordinate amounts."
Compounding can be done if patients require a custom modification to the medication, possibly because they have an allergy to one of the original version's ingredients or need a liquid instead of a pill.
"It's like going to a bakery, and you want chocolate cupcakes with white icing. We make those," said Jennifer Burch, the pharmacist and owner of Central Compounding Center in Durham, where Kessler sends her patients for compounded tirzepatide. "If you want vanilla cupcakes with blue icing, we can make that."
Her pharmacy even makes medication for pets and customizes the flavor based on animals' preferences: fish, chicken, or even bubble gum in one instance.
"I'm like, how did you figure out the cat likes bubble gum?" Burch said.
Lately, Burch's staff has been working overtime to produce tirzepatide and semaglutide, she mentioned. In the past six weeks, they've filled around 900 prescriptions for compounded tirzepatide and 500 for compounded semaglutide, utilizing ingredients purchased from chemical suppliers who, according to Burch, validate their products through compendial testing to ensure they meet quality standards.
For compounded tirzepatide, Burch's pharmacy charges between $200 and $400 a month, depending on the dosage.
Without insurance, Mounjaro costs $1,069 per month, and Zepbound is $1,060, as stated by Lilly. The company offers a savings card for Zepbound to bring the cost down to approximately $650 a month for patients with commercial insurance that doesn't cover the drug.
In August, Lilly introduced more affordable versions of its lower doses of Zepbound in single-dose vials. Patients need to draw up the medication and inject it using a needle and syringe. Regular versions of the drug come in autoinjector pens.
The vials are available for self-payment through LillyDirect, a program that facilitates access to doctors and delivery of medications to patients. They cost $399 for the lowest dose for a four-week supply or $549 for the next dose higher – the one McCaskill is on.
“Many of us won’t be able to afford to keep paying that,” McCaskill said.
‘Price is not a reason’
The number of people using compounded tirzepatide and semaglutide isn't clear, as prescriptions aren't tracked through conventional channels, Seigerman, an analyst with BMO Capital Markets, explained. Some estimates put compounded prescription rates as high as 20% for both drugs.
Brunner, CEO of the Alliance for Pharmacy Compounding, estimated that millions of people may be using compounded versions – and many may not be able to switch.
“Price is not a justification for dispensing a compounded medication, but the truth is, many patients were able to afford the compounded versions of tirzepatide, and they’re unlikely to be able to afford the FDA-approved drug,” Brunner said.
Brunner's organization requested a minimum of 60 days before compounding must cease to “ensure continuity of patient care.” He reported that numerous member pharmacies hadn't received branded tirzepatide products through their systems despite the shortage ending.
The FDA acknowledged in its statement about the tirzepatide shortage ending that “patients and prescribers may still experience occasional localized supply disruptions as the products work their way through the supply chain from the manufacturer and distributor to local pharmacies.”
In response to a request for a 60-day buffer, the FDA declined to discuss interactions with firms.
Although compounding has enabled access for individuals who might not have been able to find or afford the actual medications, the practice carries risks since it's not regulated by the FDA like branded and generic pharmaceuticals.
“Doctors ask me all the time, ‘How do I know the compounded version my patients are receiving is safe and effective?’ And I respond, ‘You don’t,’” said Fitch, chief medical officer of care provider Knownwell and past president of the Obesity Medicine Association. “This is the problem with it from the beginning.”
The FDA has warned about dosing errors with compounded semaglutide products, including some that led to hospitalization, and that some products sold by compounders used salt forms of semaglutide, which are “different active ingredients than those used in the approved drugs.” It also warned about counterfeit drugs and medications sold that are falsely labeled “for research purposes” or “not for human consumption,” which could be harmful.
And Lilly and Novo Nordisk have taken legal action against some med spas, weight loss clinics, pharmacies, and others selling compounded products, which the companies say pose “significant risks to patients.” This week, Novo Nordisk published a study it conducted in the journal Pharmaceutical Research, stating that it found impurities and lower concentrations of active ingredients in some compounded versions of its drugs.
The end of compounding GLP-1s?
The end of the shortages seems unlikely to bring about the complete end of compounding the medications. Semaglutide remains on the FDA's shortages list in the lowest dose of Wegovy, the version approved for weight loss. Novo Nordisk continues to invest in increasing its manufacturing capacity but hasn't specified when the shortage will end completely.
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McCaskill expressed her hope that Lilly might consider reducing the costs of their medications even further, making them more attainable for individuals relying on compounded tirzepatide due to pricing issues. Meanwhile, Fitch criticized the insufficient insurance coverage for obesity treatment.
Results from various studies suggest that an overwhelming majority of individuals who discontinue taking GLP-1 drugs witness a considerable weight increase, and McCaskill wants to avoid reverting the positive health changes she's experienced.
"I've heard some folks are attempting to divide their dosages, but I'm fearful of doing that," she stated. "I'm simply not willing to tamper with anything when everything's running flawlessly for me at 100%."
Despite losing access to the cheaper version of Mounjaro due to the FDA's announcement, McCaskill is concerned about maintaining her improved health. She has altered her blood pressure, A1C, triglycerides, and eating habits, as well as increased her physical activity.
The cost of the original Mounjaro was prohibitive for McCaskill, but she managed to afford it with the help of a manufacturer's coupon, paying around $500 each month. With the coupon program ending, she now faces the possibility of discontinuing its use.
