Are compounded “DIY” peptides the answer to the GLP-1 shortage?

Brief Overview of the Obesity Epidemic in the US

Understanding the obesity epidemic across the United States is critical for comprehending the extraordinary demand for anti-obesity medications (AOMs).

“We know that 70% or 75% of the country has a weight issue,” estimated Alexander. “There's a global epidemic around weight, and this new class of medications called incretins are also super effective anti-obesity medications (AOMs).”

She noted that GLP-1 drugs could achieve bariatric-level weight loss, which is life-changing for many people who are dealing with overweight or obesity. However, there has been a shortage because of the increased demand for these drugs and the vast number of patients who qualify for them.

“For a long time, [obesity has] been considered a vanity disease that is all about willpower, discipline and looking good. That is why, for instance, Medicare, until very recently, would not cover and still does not cover weight loss medications,” Alexander said.

However, she maintains that obesity requires a comprehensive approach that includes nutrition and nutrition counseling, physical activity, behavioral modification, and medication.

Drug Compounding

As medical professionals gain a more robust understanding of obesity, more providers are utilizing AOMs, such as GLP-1 drugs, which has contributed to ongoing shortages.

“When [a shortage] happens, the FDA lists a medication as being in shortage,” noted Alexander. “When a medication is listed as being in shortage, pharmacists can compound it to be provided when there's a shortage of the medication.”

There are two types of compounding pharmacies: 503A and 503B pharmacies.

Pharmacies with a 503A designation, also considered traditional compounding pharmacies, can compound prescriptions for particular patients based on their individual needs. On the other hand, 503B pharmacies are compounding pharmacies with outsourcing facilities that can manufacture larger batches and sell them to healthcare facilities.

“In a medical setting, if a patient needs a particular medication but is allergic to an inactive ingredient, a healthcare provider can go to a compounding pharmacist and ask, ‘Can you modify this medication to remove the allergen so that the patient can take it?’ This can be done in 503A or 503B pharmacies,” explained Alexander, outlining the traditional uses for these medications.

However, for GLP-1 drugs and similar peptides, the compounding process doesn’t quite work like that.

“It's kind of a wild west out there, and we have no idea where any of these [compounded products] is coming from,” emphasized Alexander.

The Dangers of “DIY” GLP-1s

While compounding can be very beneficial for some other medications, there are multiple ongoing issues in compounded peptides.

“DIY” GLP-1 drugs can also be referred to as compounded GLP-1 drugs or compounded peptides. Compounded peptides are a multifactorial category of compounded medicines; however, in the case of compounded incretins, there are GLP-1 drugs and tirzepatide, which is a GLP-1 drug combined with a glucose-dependent insulinotropic polypeptide (GIP).

She noted that there is a “gray” or black market of people selling these compounded medications to patients who cannot access the drugs from a manufacturer for a variety of reasons, including cost, insurance coverage, and drug shortages.

“There are pharmacies that are not licensed to do this. There are bootleggers who are taking advantage of the shortage by providing these medications without a license,” she continued. “These are very expensive medications, so a lot of money can be made in this black market.”

Beyond a lack of consumer awareness, Alexander also points out that many medical providers are not entirely aware of the illegal nature of these compounded drugs.

The potential for harm with these unlicensed compounded drugs is significant. The best-case scenario with these compounded peptides is that they are somewhat effective for weight loss because they contain an active ingredient that works, even if it's not a GLP-1 drug.

On a different note, the effect of these compounded medications could be neutral. Patients may wind up wasting their money and not getting the intended result because the compounded drug doesn’t contain an active ingredient.

“They can also cause much harm since it's not a regulated market. [Patients] might be getting a medication that has been taken off the market and can cause weight loss but could also cause a heart attack or [other complications],” Alexander added.

“Buyer beware,” she emphasized. “This can be very, very detrimental.”

Addressing Ongoing GLP-1 Drug Shortages

Alexander notes that avoiding compounded drugs doesn’t address the more significant issue of drug shortages, which are unlikely to last forever but remain a frustrating challenge for patients and their providers.

"Guidance is needed from the FDA," Alexander explained, "which lists the drug shortages and is responsible for managing what happens in that sector. The FDA right now, I imagine, is trying to figure out what to do since these are not niche medications."

Rather than compounded medications for a rare disease, there are vast numbers of patients across the US who require AOMs.

"The two manufacturers of these medications are stating that they are not supplying the API to anyone. Given this information, if compounders lack the active pharmaceutical ingredient to produce the compound, how could they make it? From a legal and FDA standpoint, the implications are unclear. However, it's safer to assert that, at present, compounded peptides claiming to be semaglutide or tirzepatide cannot be trusted. There's uncertainty about their composition, and they may pose risks or prove ineffective, potentially wasting your money," concluded Alexander.