Starting in 2022, high demand led to shortages of semaglutide injections sold by Novo Nordisk under the brand names Ozempic and Wegovy, as well as tirzepatide injections Zepbound and Mounjaro from Eli Lilly.
“Once patients found out how effective these medications were, word of mouth really drove up demand and outpaced the ability of these drug companies to manufacture them,” says Nate Wood, MD, a primary care doctor and co-leader of the weight management clinic at the New Haven Primary Care Consortium, part of Yale New Haven Hospital in Connecticut.
When the FDA determines a patent-protected drug is in shortage, pharmacies are permitted to compound copies of the drug. Compounding is when a licensed pharmacist combines, mixes, or alters the active ingredients of a drug to create a medication that is tailored for the needs of an individual patient.
“The very high demand combined with the very high prices and limited insurance coverage for these weight loss drugs drove the rise of the market for compounded GLP-1s,” says Mike DiStefano, PhD, an assistant professor at the Center for Pharmaceutical Outcomes Research at the University of Colorado in Anschutz.
FDA Warns About Dangers of Compounded Medications
Compounded versions of these medications helped fill the gap created during the shortage and have helped some people afford the medications who might not otherwise, but it was a “highly imperfect solution,” says Dr. Wood.
“I think that there is general agreement that these medications cost too much and not enough people have access to them, but I think very few people think that compounding them solves the problem due to the safety risks,” he says.
- Unapproved drugs aren’t FDA-reviewed. Unlike branded or even generic versions of drugs, compounded drugs haven’t been tested for safety or effectiveness by the FDA.
- Overdosing is a risk. There have been reports of people accidentally taking a much larger dose than intended of compounded semaglutide or tirzepatide, leading to side effects like nausea, vomiting, and diarrhea — sometimes so severe that they required hospitalization.
- Compounded GLP-1s may include unapproved ingredients. For example, some compounded versions of GLP-1s include the investigational drug retatrutide, which is illegal for compounding and hasn’t been FDA-approved.
- Salt forms of semaglutide are problematic. Some compounded versions use salt forms of semaglutide, like semaglutide sodium or semaglutide acetate. These aren’t the same as the active ingredients in the FDA-approved drug — and it’s not clear that these versions would have the same safety or effectiveness.
- Some versions are counterfeit drugs. Counterfeit Ozempic and other GLP-1 drugs are circulating. Unlike compounded drugs, counterfeit drugs “could contain the wrong ingredients, contain too little, too much, or no active ingredient at all, or other harmful ingredients, and are illegal,” the FDA said.
- “Research use only” products aren’t meant for humans. Some companies illegally sell unapproved drugs labeled for research, which could be harmful if used for human consumption.
“For many people, these drugs may work similarly to the branded products. However, depending on where the semaglutide is sourced from and the quality of the compounding, results will certainly vary,” he says.
The most common adverse effect that DiStefano observed are dosing errors. Because people need to use syringes rather than an auto-injector pen, they may run the risk of overdosing, which is “extremely unpleasant and could land someone in the hospital,” he says.
Still, the FDA said that, “Many of the adverse events reported for compounded products appear to be consistent with adverse events related to the FDA-approved versions of these products. ”
What the FDA’s Rule Means for Compounded GLP-1 Access
Will the rule mean that all access to compounded versions of GLP-1s will go away? That’s unclear and will depend on a few factors, experts say.
Even when there’s no drug shortage, pharmacies are allowed to compound patient-specific formulations of a drug to meet their unique needs, says DiStefano.
“For example, if a patient is allergic to an inactive compound in a drug, then a compounder may make a version of the drug without that allergen,” he says.
Although compounders can no longer produce “copies” of these weight loss drugs, there is definitely a chance that the med spas and telehealth companies that sell these drugs may continue to (or pivot to) offer “custom” compounded options by offering specialized dosages or combining them with vitamins, says DiStefano.
“However, because individual prescriptions are required for these, these companies will need to work with prescribers willing to write those prescriptions,” he says.
There are companies that are making a lot of revenue by prescribing compounded versions of GLP-1s, and they might try to find some way to continue to do that, agrees Wood.
“But I don’t think that the FDA is going to be in favor of that, and I suspect those companies will have limited success,” he says.
Will I Have to Start Back at the Lowest Dose if I Switch From a Compounded to a Brand Name GLP-1?
For people who are prescribed a GLP-1 and are able to afford it, the starting dose on the branded medication may need to start at or near the lowest dose, depending on the provider.
But that doesn’t necessarily need to be the case, says Wood.
“Obviously, people need to work with their doctor on what the starting dose needs to be. I don’t have any patients on a compounded GLP-1, but if I did, and they were taking a pretty high dose, there would be many factors we would discuss. I’d ask questions like how long they’d been taking that dose, what their side effects were, and then we would come to a decision together about what dose to start. In most cases, I don’t think I would have them restart from the lowest dose,” he says.
Expert Advice for People Who No Longer Have Access to GLP-1s
Talk with your doctor, says Wood.
“If you’ve been taking the medication to treat obesity, the research says that the weight will probably start to come back, often pretty quickly,” he says.
First check and see if getting the branded version is a possibility — your insurance may have changed, or you may be able to afford it out-of-pocket. Although the drugs are still pricey, the costs for some brands have dropped significantly since they were first introduced, says Wood.
“If that’s not an option, there are other FDA-approved medications that may not be as effective as newer generation GLP-1s, but they may still prevent that weight from coming back,” he says.
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