Demand for popular weight loss drugs such as semaglutide and tirzepatide (Wegovy and Zepbound) has long outpaced supply, forcing many patients with obesity to visit compounding pharmacies for their medications.
Confusing regulations and headlines have left many people unsure of the safety of these products, which are regulated differently than their name-brand counterparts. Shauna Levy, MD, an assistant professor of surgery at Tulane University Medical Center and medical director of the school’s Bariatric and Weight Loss Center, sat down with WebMD to discuss how patients can navigate this evolving landscape.
Editor’s Note: This interview has been edited for length and clarity.
WebMD: Why is compounding allowed for GLP-1 medications such as semaglutide, and tirzepatide?
Levy: Compounding pharmacies are allowed to make any number of pharmaceutical medications when those medications are on the FDA’s shortage list. When GLP-1 medications were first introduced for obesity, they took off like wildfire. It was all over social media and really the press. Basically, everybody wanted to get their hands on them.
When demand outstripped supply, they went on the FDA’s shortage list and compounders were allowed to make them. Part of the problem was that the makers of Wegovy had some issues with their factory.
WebMD: Tirzepatide was recently removed from the FDA shortage list. What does this mean for patients who were getting it from compounding pharmacies?
Levy: This is complicated because, technically, the compounding pharmacies are no longer needed to bridge the gap, so they're not supposed to make compounded tirzepatide anymore. But there is an access issue. A lot of insurance doesn’t cover anti-obesity medications of any kind, not just the GLP-1s. There are a lot of patients that have been getting access to a more affordable product, rather than paying for the FDA-branded medications.
I talked to a couple people who either run compounding pharmacies or have practices that use compounding pharmacies, and I guess as long as they sort of change the dose outside of the standard of the dosing for tirzepatide, they think they'll be able to still sell it. I'm also seeing there's still a shortage for patients, even if it's not on the FDA shortage list. I guess it remains to be seen – because this is a recent change of taking it off the shortage list – as to what's going to happen. Eli Lilly (maker of tirzepatide) is already sending out cease-and-desist letters to compounding pharmacies.
(Editor's note: Two weeks after removing it, in response to intense public pressure and a lawsuit, the FDA agreed to reconsider this decision -- allowing compounders to continue making tirzepatide, at least in the short term.)
WebMD: Some experts say compounding drugs such as semaglutide and tirzepatide isn't safe. Others say it's basic chemistry for any skilled pharmacist. What's your view?
Levy: My view has evolved, if I'm being honest, because at first all my information was coming from Novo Nordisk (maker of Wegovy), which was saying, “This is bad. This is bad. This is bad. Where are they getting their products? They’re getting bootleg products.”
I'm not a chemist, so I can't honestly comment on whether it's simple chemistry, but I do know that there are compounding pharmacies that do quality and safety checks. Now, the thing that makes me nervous is when these products are mixed with other additives, like B12, or they were putting salts in there in a way that wasn't studied. That part gives me pause. But whether or not it could be made safely and then whether they can check the quality and the integrity of the product – I believe that can be done in the compounding pharmacy.
WebMD: Tell us about the manufacturing differences between name-brand semaglutide and tirzepatide versus the compounded alternatives.
Levy: It really is the batch and the scale, because each compounding pharmacist can kind of do their own thing. Some of these bigger compounding pharmacies are doing it in larger-scale factories, maybe not to the degree of Novo Nordisk, but they are making larger batches. They're doing it also in a different way. They're not doing it in the prefilled pens. They're doing it in vials, which makes it a little bit different.
WebMD: Novo Nordisk recently published a peer-reviewed study saying several compounded versions of semaglutide were of “markedly lower quality” than its version. Does that worry you?
Levy: You might be getting good stuff. You might not. You don't know. You can't read the ingredients on the package, right? That doesn't mean it's unsafe. But there are patients who say, “Oh, that medication never worked for me.” Well, did it not work for you because the product was less potent? Or it was somehow made inconsistently? Or was it not effective for you, period? It's really hard to say.
A person who's really pro-compounding might say: Big factories and big companies like Novo Nordisk make mistakes, too. They also are not perfect. They have recalls. And the benefit of compounding is the small scale. Because if one compounding pharmacy makes a mistake, it has an issue. It doesn't mean all compounding has an issue.
WebMD: Does some insurance cover compounded GLP-1s?
Levy: Yes, but often people don’t realize it. I've seen a ton of patients in my clinic that actually did have insurance coverage and were paying $200, $300 a month for compounded products when nobody mentioned to them that they should check with their insurance. There's so much misunderstanding about whether or not they have insurance coverage, they probably just assume they don't have insurance coverage and they don't check.
WebMD: Is there anything a patient can do to vet a pharmacy that compounds medications?
Levy: When you are looking for a pharmacy, start with your doctor for a recommendation. I would ask your friends and family who they're using, too: if they've had success, if the medicine has been effective, if they've been happy with the outcome. Obviously, it doesn't guarantee safety or success, but it's better than going to a place where people got sick or the medicine didn't work or you're just completely in the dark. Beyond that, there is a certificate (of analysis) that the pharmacies have that shows that their products are up to safety and quality standards. I think that the patient should ask to see it.
WebMD: How do delivery systems for Wegovy and Zepbound differ from those of their compounded counterparts?
Levy: Compounded versions use multiuse vials. Wegovy and Zepbound use prefilled syringes – single-use pen injectors. You just take off the cap and put it on the spot and click it like a pen and wait for the medicine to go in. It's so easy. It's really nice for the patient and makes it pretty foolproof.
I've heard of patients who accidently get the wrong dose because they use a partner’s prescription instead of their own. Other than that, it's very difficult to get the wrong dose.
But that delivery system also makes it more expensive. Eli Lilly has recently released a more affordable version of (Zepbound), giving it in vials. It’s only the 2.5- and the 5-milligram doses. They're not doing the higher doses, I think, because they don't want people to buy 15 milligrams and then partition it out to make it even more affordable. But they're basically copying the compounding pharmacies now and selling vials.
I have not heard of compounding pharmacies using a pen injector. I've seen commercials where it looks like they have an off-label pen injector, so maybe some pharmacies do. But the ones that I've seen or heard of are vials, which, honestly, makes more sense. That's a lot more affordable.
WebMD: Do compounded injectable drugs such as semaglutide pose additional safety concerns in terms of sterility or dosing?
Levy: When they give you a multiuse vial – as often happens with compounded variations – every time you reuse a vial, you're exposing yourself to the possibility of getting an infection, or overdosing or underdosing really. We sit here in the clinic and explain to people how to use medications, and then they leave the clinic and they're so confused. Obviously, when the patients receive the injections in the clinic, there's a lot less room for error than if they have to go home and do it themselves. But it's also a pain in the butt. It's a burden. It's an inconvenience to have to go to the clinic every time you want to get an injection.
WebMD: Poison centers say they’ve experienced a 1,500% increase in calls about accidental semaglutide overdose. How can patients avoid this type of mistake?
Levy: First of all, people are not necessarily going just to compounding pharmacies. They may be going to med spas or some different providers that may not operate under safe oversight and in some cases aren’t even legal. You need to be really careful about where you buy your products and that you're seen by some sort of medical professional that's really guiding your care.
I've heard of some places where you go and order like a menu what dose you want. That seems really problematic because I think that some people don't understand that you have to work your way up in the dosing. You have to start with the lowest dose and make sure your body tolerates it before moving up to a higher dose. Even with the name-brand medicine, if you take too high of a dose, you're going to feel super-duper sick, and sometimes for up to a month.
WebMD: How important is it for patients to consult their doctor or primary care physician before pursuing compounded weight loss medications?
Levy: That's so tricky because sometimes – I don't mean to sound insulting – but doctors aren't trained on this. I would say consult somebody who has expertise in treatment of obesity, which may or may not be your primary care physician. I think it's important to connect with a medical professional, but that doesn't mean that all primary care doctors or doctors in general have expertise in treating obesity.
You’re definitely better off with an obesity specialist. You can go to the American Board of Obesity Medicine website and search for a physician who is board certified. That doesn't mean your primary care doctor is not the right person, but just because they're your doctor doesn't mean they have expertise in treating obesity. Frankly, it's the medical schools’ fault. We're not taught about this.
WebMD: Some outlets advertise compounded oral versions of Wegovy, which the drugmakers say are not legitimate. Do you have any experience with these versions?
Levy: I would not recommend them. We have an oral version. It's Rybelsus. We don’t know anything about these different formulations – sublingual variations – that are just completely changed. I even saw a pharmacy selling (the experimental weight loss drug) retatrutide, which is the next iteration that’s going to make it to market in I don’t know how many years. That feels wild that pharmacies are selling variations of drugs that aren’t even on the market. Whether it’s retatrutide or sublingual semaglutide, I would not recommend it for my patients. I would stick to the ones that we have more experience with. We now have at least a year or two of experience of patients using compounded semaglutide or compounded tirzepatide.
WebMD: A lot of the warnings about the compounded GLP-1s have involved med spas or little-known online outlets. How big a problem are these sorts of businesses?
Levy: I think it's a real problem. Obesity has been outsourced to industry for so long that doctors have not been treating obesity – it’s been Weight Watchers and Jenny Craig and SlimFast and all these businesses. But obesity needs to be treated by a medical professional because it is a disease, just like high blood pressure, diabetes, cancer, etc.
When med spas or little-known online outlets are selling these products, they're once again hijacking the treatment of the disease of obesity. It's showing insurance companies that this doesn't need to be treated by a doctor. You can just buy it at any bodega on the street. That's a problem when we're trying to treat one of the worst epidemics in our country.
WebMD: Med spas and shady websites aside, what about more established companies? You mentioned Weight Watchers, but there are many – Ro, Hims/Hers, PlushCare, Noom – advertising GLP-1s with a telemedicine visit. Should patients trust products from these types of businesses?
Levy: I personally would opt for somebody I could see in person and talk to the pharmacy where my product is coming from. I'm not anti-telemedicine, but many of these places can be more expensive than just going to a local physician. I couldn't recommend using them because I think that they have dual motives. They're not just trying to sell you a product. They're trying to sell you counseling and all these other components. If there's a problem, I don't know how you would connect with a doctor or a medical professional.
