Compounded medications are safe — if you know where the ingredients come from. In this case, we don't.
Semaglutide, the first FDA-approved obesity drug since 2014, has been surging in popularity.
Medical experts have deemed the injectable drug a "game changer" in the science of weight management, while social-media users have embraced it as a trendy diet drug, with high-profile users like Elon Musk and rumors of extensive use among Hollywood celebrities.
But almost as quickly as it burst onto the global market, semaglutide became difficult to get.
Just months after the June 2021 approval of Wegovy, the version of the drug that's intended to treat obesity, providers were reporting inadequate supplies. The shortages also affected the availability of semaglutide for type 2 diabetes treatment, for which it was originally approved under the brand name Ozempic.
Since patients need to continue taking semaglutide to maintain its weight-loss benefits, that's a major obstacle. So is the out-of-pocket monthly cost of $1,349 for Wegovy and $892 for Ozempic, which is rarely covered by insurance.
As a result, patients seeking the drug via Google search are met with an appealing alternative: compounded medication, which is available online or administered in a doctor's office, and typically advertised for a fraction of the brand-name price.
A compounding pharmacy typically crafts prescription medications to fit a patient's unique needs, offering them in a different dose, form, or with alternative ingredients than brand-name versions. The practice is as old as pharmacy itself, and is generally considered safe and effective by physicians.
But in the case of compounded semaglutide specifically, it's difficult for patients to know what they're getting, and how safe and effective it might be, said Dr. Christopher McGowan, a gastroenterologist and obesity medicine specialist.
That's because the drug's manufacturer, the Danish pharmaceutical company Novo Nordisk, has a patent on the semaglutide molecule, making it the sole source for compounding pharmacies. And the company has made it clear: It doesn't sell semaglutide for compounding.
That's led to a great deal of confusion about where, exactly, compounding pharmacies are sourcing the drug — or if what they're selling is even semaglutide at all.
On top of that, compounded versions of semaglutide may be further altered from the brand-name versions. They could be diluted, making them less effective, or blended with other ingredients, such as B vitamins, in formulations that haven't undergone rigorous testing.
"In theory, someone could make it right, if they're getting it from what I would consider a reliable compounding pharmacy," Dr. Scott Isaacs, an endocrinologist and obesity medicine specialist, told Insider. "The problem is there's no oversight, there's no way to verify."
Compounded medications are well-regulated and generally considered safe — but semaglutide is an unusual case
McGowan said he first noticed growing interest in compounded semaglutide about a year ago. "It's something that I'm asked about multiple times a day, by patients and people who reach out to me," he told Insider.
Compounded medications essentially take the active ingredient in a prescription medication and customize it to a specific patient's needs, said Tenille Davis, a compounding pharmacist at Civic Center Pharmacy in Scottsdale, Arizona.
For instance, a compounding pharmacist could make a medication easier for an infant to swallow by turning it into a liquid, rather than a pill. They can customize medications to be free of common allergens, like peanut oil, or animal products that violate patients' dietary restrictions, like gelatin.
There are about 7,500 compounding pharmacies nationwide, representing roughly 13% of the total number of US pharmacies, according to the American Pharmacists Association.
"We fill spaces in the market that aren't filled by drug manufacturers. There are lots of reasons for compounding," Davis told Insider.
While compounded drugs are not FDA-approved, the agency requires compounding pharmacies to work within strict federal and state regulations, said Scott Brunner, the CEO of the Alliance for Pharmacy Compounding, an industry trade group.
All drugs that can be compounded have to be either an active ingredient in an FDA-approved medication or recognized by the US Pharmacopeia. Compounded versions of injectable drugs like semaglutide are subject to even stricter scrutiny, since they have to be prepared in a sterile environment for safety reasons.
The law generally prevents compounding pharmacies from making identical copies of commercially available drugs. But an exception exists when the FDA puts a commercial drug on its official list of shortages. Currently, Wegovy and Ozempic are on the list, making compounded semaglutide fair game as far as pharmacies are concerned.
There's just one problem: They can't actually obtain it from the manufacturer.
Typically, compounding pharmacies work with pharmaceuticals that are readily available from FDA-registered facilities in bulk, including hormones like testosterone and estradiol or common pain medications.
But unlike those drugs, semaglutide is a patented molecule, which means the entire supply comes from just one manufacturer: Novo Nordisk. No FDA-approved generic versions exist.
"You can't buy the raw ingredients. It's only Novo Nordisk making it," Isaacs said.
And Novo Nordisk said it's not providing the drug to compounding pharmacies at all.
"We do not sell semaglutide for the purposes of compounding with other products, and we have not conducted studies to evaluate the safety and effectiveness of semaglutide when compounded with other ingredients," a Novo Nordisk representative told Insider.
Brunner said that some compounding pharmacies have even received cease-and-desist letters from Novo Nordisk, arguing that selling compounded semaglutide infringes on its intellectual property — despite the fact that FDA regulations currently allow it. The company declined to comment on specific legal actions.
Where is compounded semaglutide coming from?
Pharmacies need to get semaglutide from an FDA-registered source in order to compound it. But if its sole manufacturer isn't cooperating, doctors have major questions about where it's being sourced.
"We don't know if it's semaglutide at all, unless someone is clear about where they're sourcing it," McGowan said. "Perhaps it is — but is it of the same potency and quality, and does it have the same effect?"
One explanation, Isaacs said, might be that suppliers are buying the brand-name versions of the drug in their highest-dose formats, then repackaging them into smaller doses. "If it's real semaglutide, they're getting the pens and separating it out."
That could explain how they're able to offer it at a significantly lower cost. Some websites list compounded semaglutide for $300 a month, compared to the $1,300 price tag for Wegovy.
But if patients are paying less, they may be getting less of the medication, too, or a version diluted with unknown additives, Isaacs said. Some versions of compounded semaglutide include additives like B vitamins, which are advertised as further aiding weight loss or reducing common side effects, like nausea.
"Those combinations have never been studied. We don't know if adding the other components alters the medication," McGowan said. "There's a lot of ifs. I would not be willing to risk my patients."
Some purveyors of semaglutide may also be selling a different pharmaceutical, known as semaglutide sodium, said Samantha Blakeney, the vice president of new business and marketing at VLS Pharmacy and New Drug Loft Pharmacy, a compounding pharmacy in New York.
Semaglutide sodium is a research product that breaks down into semaglutide base and is available to purchase online, sold as "not for human use." It isn't quite the same thing as semaglutide, since it hasn't received the same FDA testing and approval, Blakeney said.
The APC has issued a warning to its members that semaglutide sodium "should not be used in human drug compounding." But some bad actors in the industry may be doing so anyway.
And unfortunately, FDA enforcement in this arena is lacking, said healthcare attorney Harry Nelson, of Nelson Hardiman LLP.
"It's a very under-regulated area," he said. "Until something happens and someone gets hurt, the FDA doesn't have the bandwidth to enforce it."
People have also reported sourcing semaglutide without a prescription through international pharmacies, in which case there may be no regulation at all.
Online clinics are helping patients get the drug with little oversight, worsening shortages
Compounding pharmacies fill prescriptions for patients, but they can't always verify each patient is working with trustworthy prescribers and getting appropriate follow-up care.
Semaglutide is intended to be prescribed by obesity doctors, either for people with a BMI of 30 or higher, or a BMI of 27 and related complications.
That's so doctors can monitor the drug's side effects and make adjustments if needed to ensure its safety and effectiveness, Isaacs said. They should also work with patients on related lifestyle changes, like a good nutrition plan and exercise.
But as semaglutide's popularity grows, some providers are cutting corners, requiring only a single online visit to obtain a prescription.
According to Davis, there are "many, many patients" who are getting semaglutide prescriptions through a single online form or telehealth visit, without the recommended follow-up with a doctor.
"They don't have obesity, they don't have diabetes, they're looking to lose a few pounds," Isaacs said. "I saw a patient yesterday who didn't need to lose anything, and had been taking it for a month. It's easy, they go online, they make an appointment, they don't have to go anywhere or tell the truth, they can just get it."
McGowan said these off-label, cosmetic uses of semaglutide have worsened shortages and are distracting from the therapeutic importance of the medication.
"The messaging has been derailed from this being a medical breakthrough to a celebrity short-term weight-loss drug. It's not a quick fix," he said.
Compounded semaglutide could become illegal — but that may not stop it from being sold online
Novo Nordisk recently announced that Wegovy was once again available to providers, which Isaacs and McGowan confirmed. However, semaglutide remains on the FDA's shortage list, meaning compounded pharmacies are still legally allowed to provide it. Once it comes off, patients should, in theory, only be able to access the brand-name sources of the drug.
But because of the high cost of semaglutide, patients will likely continue to seek discounted or more easily accessible versions of the drug, according to Isaacs.
"The issue is more than the shortage, the issue is insurance coverage," he said. "There's a temptation to do something that may seem easier or cheaper, but in my experience, it's not either of those things. People spend a lot of money and get nothing."