The truth about GLP-1 compounds that doctors need to know

As a cardiologist specializing in obesity medicine, I often encounter patients who would greatly benefit from the new generation of weight loss drugs that work as glucagon-like peptide 1 (GLP-1) agonists. In the recently published SELECT trial results, for example, semaglutide (marketed by Novo Nordisk as Wegovy for weight loss and Ozempic for type 2 diabetes) demonstrated a 20% reduction in the risk of attacks heart and cerebrovascular accidents in overweight and obese people without diabetes and with cardiovascular disease. disease, establishing it as a cardiovascular disease-modifying drug in people without type 2 diabetes.

Unfortunately, the high demand for these new weight loss drugs has resulted in a frustrating and lasting shortage. The makers of the two FDA-approved drugs, Novo Nordisk and Eli Lilly (tirzepatide, marketed as Zepbound for weight loss and Mounjaro for type 2 diabetes), are struggling to meet the overwhelming need.

To ensure continuity of patient care, federal law allows compounding pharmacies to “substantially copy” drugs listed as “currently in short supply” on the Food and Drug Administration’s Drug Shortage List Administration (FDA) of the USA. Both semaglutide and tirzepatide are on this list. For Americans suffering from obesity and other weight-related diseases, these drugs could be a lifesaver.

Despite this, the medical community has widely criticized the use of compound GLP-1 agonists, even those obtained from legitimate and reputable compounding pharmacies.

Yes, the high demand has led to the emergence of unregulated and fraudulent companies that produce substandard or counterfeit versions of these drugs.

The FDA has found fraudulent products (disguised as weight loss drugs) and issued warning letters to stop the distribution of illegally marketed semaglutide. “These medicines can be counterfeit, which means they could contain the wrong ingredients, contain too little, too much or no active ingredient, or contain other harmful ingredients,” he warns. Some products use a similar-sounding semaglutide sodium salt, which has uncertain safety and efficacy and has drawn warnings from the FDA and state boards of pharmacy.

Many of these products are marketed directly to consumers online through websites and social media, with little or no medical oversight. This practice is a major concern as it can affect patient safety and should be discouraged.

However, according to a statement from the Alliance for Compounding Pharmacy (APC), legitimate compounding pharmacies are not the ones selling these dubious products on the black market, especially online. This illegal practice has attracted media attention and is sometimes incorrectly associated with legitimate pharmacy compounding.

In contrast, legal and certified versions of GLP-1 agonist medications can be obtained from well-regulated and reputable compounding pharmacies. These pharmacies must adhere to all federal and state regulations and dispense drugs only with a valid prescription from a licensed physician.

Meanwhile, according to the APC statement, Novo Nordisk and Eli Lilly have sued compound companies in several states, questioning, among other things, the purity and potency of some compound products.

There are different designations for compounding pharmacies: 503A and 503B. 503As are state-licensed pharmacies and physicians, and 503B pharmacies are federally regulated outsourcing facilities that are strictly regulated by the FDA. This regulation, established in the wake of a 2012 outbreak of fungal meningitis linked to a compounding pharmacy, ensures higher quality control and oversight, especially for drugs intended for intravenous or epidural use. These standards exceed those required for subcutaneous injections such as GLP-1 analogues.

Faced with this Wild West climate, where compounded drugs can vary in their source, formulation, potency and purity, The Obesity Society, the Obesity Medical Association and the Obesity Action Coalition released a joint statement discouraging the use of compounds. GLP-1 agonists, citing safety issues and lack of regulatory oversight.

This stance, while intended to ensure patient safety, inadvertently raises a critical issue.

By dismissing compounded drugs entirely, practitioners may inadvertently bolster the black market and overlook the needs of patients who could benefit from these drugs, contrary to the intent of the federal law’s exemption for combination during a drug shortage. In fact, the presence of unreliable providers highlights the need to direct the public to reliable sources, rather than imposing a blanket ban on medically appropriate alternatives.

The joint statement says compound GLP-1 agonists are “counterfeit.” This inaccurate overgeneralization likely stems from a misunderstanding of the composition process and its regulations. Legitimate, regulated pharmacies compound stock GLP-1 agonists, which are “essentially a copycat” of FDA-approved drugs, not counterfeits. Recognizing this is crucial to maintaining trust in both compounding pharmacies and regulatory bodies.

It is correct that “the only manufacturers of these drugs approved by the FDA are the companies that created the active pharmaceutical ingredients Novo Nordisk and Eli Lilly”, but the joint statement does not mention the exemptions provided by the law that allow combining copies of the drugs of brand if they are on the shortage list.

Compounding pharmacies must source active pharmaceutical ingredients (APIs) from FDA-registered facilities, which must adhere to current good manufacturing practices (cGMP). This ensures the quality, potency and purity of APIs, crucial to the safety and efficacy of compounded medicines.

Compounded medications are not FDA approved, but they are not inherently unsafe. Compounded medicines include critical drugs such as resuscitation drugs and antibiotics, and are often used in healthcare settings, especially when there are shortages. This raises the question of why compound GLP-1 agonists would be treated differently in these scenarios.

And in the case of alternative drugs for people with obesity who are at higher risk of cardiovascular disease, the FDA-approved brand-name alternative may be of more concern than the compound GLP-1 agonist. Obesity societies advise: “If you cannot find or access a GLP-1-based treatment now, there are other treatments available,” experts echoed. Although the statement does not specify the names of the alternatives, experts have advised using alternatives such as Qsymia and Contrave, despite their potential cardiovascular concerns. This recommendation to the public may not represent a responsible risk-benefit analysis.

Instead of banning GLP-1 compound medicines entirely, expert associations can contribute to the solution by creating a “seal of approval”, recognizing high-quality compound medicines. This would contribute to informed decision-making for doctors and patients.

Possible Solutions

When prescribing GLP-1 agonists for the treatment of obesity, clinicians should consider all of the following steps to ensure patient safety and effective treatment:

Preference for FDA approved brands: FDA-approved brand-name GLP-1 agonist medications should be the primary choice because of their established safety and efficacy.

Risk-Benefit Analysis for Non-FDA Approved Products: In cases where FDA-approved options are not available, doctors may consider prescribing a non-FDA-approved copy of the brand-name drug. Before doing so, conduct a thorough risk-benefit analysis with the patient, ensuring that the patient is fully informed of the potential risks and benefits of using a non-FDA approved product.

Choose copies of semaglutide for specific cases:In patients with obesity and cardiovascular disease, the benefits of using a compound copy of semaglutide, with its cardiovascular disease-modifying properties, may outweigh the risks compared with other FDA-approved anti-obesity drugs that may carry cardiovascular risks or compared to no antiobesity treatment.

Informed consent and monitoring: When prescribing a non-FDA-approved version of a GLP-1 agonist, it is recommended that the patient’s informed consent be obtained. They should be aware of the differences between FDA-approved and unapproved versions.

Choosing between 503A and 503B pharmacies: Prescriptions for non-FDA approved GLP-1 agonists can be directed to 503A or 503B compounding pharmacies. However, it is advisable to check whether the product can be added to a 503B pharmacy, which is subject to an additional layer of FDA regulation, which provides greater assurance of quality.

Clear prescription specifications: Make sure the recipe explicitly states that the compound GLP-1 agonist should be the base compound without additives.

Application for certificate of analysis: To further ensure safety, request a certificate of analysis from the compounding pharmacy. This provides detailed information on the quality and composition of the product.

Permanent monitoring: Continuously monitor the patient’s response to medication and adjust the treatment plan as necessary, maintaining periodic follow-ups.

By adhering to these guidelines, physicians can navigate the complexities of prescribing GLP-1 agonists in a manner that prioritizes patient well-being, especially in settings where conventional treatment options are limited.

Eldad Einav, MD, is a board-certified cardiologist and board member of the American Board of Obesity Medicine. He is a Fellow of the American College of Cardiology and a Fellow of the Obesity Medicine Association. He serves as the Medical Director of Cardiometabolic Health at Guthrie Lourdes in Binghamton, New York, and is the founder of myW8/Cardiometabolic Health located in Beverly Hills, California.

This article reflects only the personal opinions of Dr Einav and should not be considered as representing the official position of Guthrie Lourdes. Dr. Einav served as a promotional speaker for Novo Nordisk in 2022. So far, he has not prescribed any compound GLP-1 agonist drugs in his medical practice.

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