Compounded Weight Loss Drugs Are Popular. But Are These Ozempic-Like Copies Safe?

Since drugs like Zepbound and Wegovy entered the weight-loss arena, and the high demand for the diabetes-turned-diet drugs pushed them into short supply, a new world centered on these medications has emerged.

Compounded versions of GLP-1 (glucagon-like peptide-1) drugs are within easier reach of some of the nearly three-quarters of Americans who are overweight or obese. With a quick online survey or jaunt to the corner “medical spa,” millions of people are receiving the often-called “miracle” drugs on their doorsteps.

But the question looms: at what cost? Are these compounded drugs – attractive for their easy access and starkly reduced prices (think $200 a month compared with $1,000-plus) – safe?

“It’s hard when you speak in absolutes, because the truth is probably somewhere in the middle,” said Gina Moore, PharmD, MBA, associate professor of the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.

Many health experts, along with the Food and Drug Administration and the American Diabetes Association, advise against the use of the compounded versions. But others, like Moore, are on the fence, given the power of the medications to change patients’ lives.

“But the challenge is: How do you distinguish between a good pharmacy and somebody that might not be acting in the best interest of the patient?”

 – Gina Moore, PharmD, MBA

“There are good, legitimate compounding pharmacies that are out there filling the need and making these products available,” said Moore, senior associate dean of operations and regulatory affairs. Moore has maintained a close eye on the evolution of the drugs, from lawsuits filed by manufacturers over compounded replicates to clinical trials of newer GLP-1 options on the CU Anschutz Medical Campus.

“But the challenge is: How do you distinguish between a good pharmacy and somebody that might not be acting in the best interest of the patient?” she said.

Moore shared highlights of what consumers should know, addressing some of the FDA concerns about fake products, lack of sterility, adverse events and dosing errors within the burgeoning compounded drug scene.

Know the reason for the compounded market’s rise

Manufacturer shortages arose in 2022 and are only recently beginning to end for the brand-name weight-loss drugs, whose active ingredients include the still-plentiful semaglutide and tirzepatide. “These manufacturer drugs are packaged as an autoinjector pen, and it’s really the pen device that became in short supply,” Moore said. So, the FDA at that point allowed compounding.

When a commercially available drug that is on patent is in shortage, that allows compounding pharmacies to make a copy of that drug to meet the need. Compounding pharmacies are required to use the active ingredients of a drug being replicated and are subject to oversight by their respective state board of pharmacy and/or FDA. But compounded products are not required to undergo safety and efficacy testing in human subjects.

“It’s a buyer-beware market,” Moore said of the market that mushroomed in the past two years.

In a recent study, Moore and colleagues, including lead author Michael J. DiStefano, PhD, assistant professor of clinical pharmacy, identified 93 direct-to-consumer business websites advertising compounded GLP-1 products for weight loss in Colorado. Most businesses are self-categorized as medical/health spas (33) or weight-loss services (26).

Be aware of delivery modes’ increased risks

The compounded products come in multi-dose vials with syringes rather than the autoinjectors manufacturers use that are individually dosed for the patient. “So, you have to pull up the dose and inject it, which has led to dosing errors,” Moore said. The FDA has received reports of overdoses, with cases of people administering five to 20 times more than the intended dose of semaglutide.

Adverse events even with proper dosing also happen (as they do with the manufactured drugs), and concerns focus on lack of patient oversight, especially with the estimated 11% of compounded drug users who acquire their medications via the internet.

“These drugs are not without side effects, and you have to be careful and be appropriately monitored by a healthcare provider that’s trained and experienced in managing the medications,” Moore said. “There can be nutritional issues and true adverse side effects.”

Common side effects include nausea (44% of patients), diarrhea, vomiting and constipation. Severe vomiting can occur and require medical attention. Rarer but serious side effects include pancreatitis and risk of thyroid tumors, which a doctor should monitor for during the duration of the drug’s use.

Learn how to weed out the bad actors

For people who go the compounded route, doing their homework is critical, Moore said. “It's questionable where many of these ‘med spas’ or ‘clinics’ are getting their products. So, I’d want to make sure to ask and verify,” she said. “They could be getting it and mixing it themselves (when fraud and mistakes happen), and the consumer doesn’t know that unless they dig.”

In their study of Colorado businesses, Moore and fellow researchers found numerous false regulatory claims and the use of several unapproved products, including one deemed unsafe for compounding by the FDA.

The drugs should be coming from 503A or 503B pharmacies, the latter of which are compounding pharmacies with outsourcing facilities that may manufacture large batches. “They are inspected by the FDA, so they have a higher level of accountability in terms of their manufacturing, sterility testing and authentication of the product,” Moore said.

“The FDA does not test these individual products for safety and efficacy. It’s just that they have to show that they are getting the actual ingredient that’s supposed to be in the product and do sterility testing, which is especially important when people are injecting these drugs.”

With 503A pharmacies, which compound drugs individually with a patient prescription (like a traditional pharmacy), oversight comes from the State Board of Pharmacy. “They still have to do things like a certificate of analysis indicating where they get the raw ingredient from and do sterility testing.”

Also, make sure the supplying pharmacy is registered to do business in the state, Moore said. “Many of the products are from Florida, for instance, but that pharmacy has to be registered to do business in the state of Colorado. So then, they at least have oversight and are regulated by the State Board of Pharmacy.”

Moore also advises checking the State Board of Pharmacy website (for whichever state the business resides) for consumer complaints and inspection violations.

Watch out for your health, not just your pocketbook

Be wary of online sites with no medical oversight, and if possible, stick to the big players. “Some are good and, I think, are very reputable. Weight Watchers and Ro are really doing it right and partnering with good established entities and include monitoring and nutrition counseling along with access to the medication.”

Even with the bigger companies, make sure the providers are professionally trained in their areas, and that proper screening is required, Moore said. That means a person has to have a BMI of 30 or greater, or of 27 or greater with a concomitant risk factor, such as hypertension or prediabetes.

Moore noted that it’s understandable that people with persistent weight issues are attracted to the compounding world. She just urges vigilance.

“Certain drugs come along, and they change the treatment of a particular disease,” Moore said. “It feels to me like GLP-1 drugs are among those. In many cases, the impact they are having on weight loss is incredible. And we’re seeing cardiovascular and other health benefits as well. They are changing the landscape and addressing obesity in a way we’ve not seen before.”