Are compounded GLP-1 drugs safe?

Surging demand for GLP-1 drugs

The recent surge in demand for GLP-1 drugs is primarily due to their effectiveness in weight management. Originally used to manage blood sugar levels in diabetic patients, GLP-1 agonists have demonstrated the ability to induce significant weight loss in clinical trials, with some patients losing up to 15% of their body weight -- a result that has been challenging to achieve with earlier medications.

"There really hasn't been a weight loss drug as effective as semaglutide or tirzepatide. GLP-1 drugs are a game changer," explained Mark Mikhael, PharmD, CEO of Olympia Pharmaceuticals. "I myself use semaglutide, and it's helped me lose 50 pounds. Doctors and patients are seeing [these results] and clamoring to get it."

The dramatic results seen in real-world use cases, coupled with clinical data supporting their efficacy, have contributed to the unprecedented spike in demand.

Moreover, emerging research suggests that GLP-1 drugs might offer additional health benefits. As a result, these medications are being prescribed off-label for a variety of conditions beyond diabetes and obesity, further straining supply chains and leaving many patients without access to these transformative therapies.

What is causing the GLP-1 drug shortage?

The current shortage of GLP-1 drugs is largely a result of manufacturers being unprepared for the sudden surge in demand. While initial production was scaled to meet a steady market for diabetes treatment, the explosion of interest in these medications as weight loss solutions has overwhelmed supply chains. Supply chain disruptions, such as raw material shortages and production delays, have only compounded the problem, leaving patients and healthcare providers scrambling for alternatives.

"The shortage of GLP-1 medications is driven significantly by an unprecedented demand that pharmaceutical companies did not fully anticipate," explained Shawn Hodges, PharmD, CEO of Revelation Pharma. "Although GLP-1s are primarily used for weight loss and diabetes management, ongoing research continues to reveal additional benefits."

For instance, a study by Dandelion Health suggests that GLP-1 drugs could help prevent heart attacks and strokes in high-risk patients without existing heart disease. Researchers estimate that 44 million people in the U.S. could benefit, potentially preventing up to 17,300 heart attacks and 16,700 strokes each year.

Another study found that GLP-1 drugs reduce the risk of 10 out of 13 obesity-related cancers compared to insulin in type 2 diabetes patients. The biggest reductions were seen in gallbladder, meningioma, pancreatic and liver cancers, with up to 65% lower risk.

GLP-1 drugs have also been shown to protect kidneys, reduce the risk of cardiovascular mortality, and lower the chances of severe outcomes and death from COVID-19. Moreover, these medications are being studied for their potential to treat mental health disorders, like depression and compulsive behaviors and for managing metabolic liver diseases.

Beyond weight loss and glucose regulation, they provide broader health benefits by decreasing inflammation, improving heart function, and offering protective effects across multiple organ systems.

"As a result, the scale of demand is far beyond what current manufacturing capacity can handle," added Hodges.

This gap in supply has opened opportunities for compounding pharmacies to fill the void, providing compounded versions of GLP-1 drugs to patients who might otherwise be left without access to treatment. However, the rapid rise in the availability of compounded versions has also brought new challenges and concerns, particularly around safety and regulation.

What are compounded drugs?

Compounded drugs are created by combining, mixing, or altering ingredients to prepare a drug tailored to the needs of an individual patient. Compounding can offer solutions when a patient needs a specific dosage not commercially available, has allergies to certain excipients in the mass-produced drug, or needs a different delivery form, such as a liquid instead of a tablet. However, compounding is not the same as mass manufacturing. It requires strict adherence to safety and quality standards to ensure that the final product is both safe and effective.

What are compounded GLP-1 drugs?

For GLP-1 drugs, compounding involves acquiring the active pharmaceutical ingredient (API) and preparing it into a customized formulation. This process must be performed in a sterile environment under strict quality control protocols to prevent contamination and ensure that the medication is consistent with what the physician has prescribed.

"One of the biggest benefits of compounding is agility," noted Hodges. "Compounding pharmacies can respond in just days or weeks, which is much faster than traditional pharmaceutical manufacturers that can take months -- even years -- to scale production."

However, ensuring that compounded GLP-1 drugs are made safely and meet regulatory standards requires specialized knowledge, equipment, and adherence to rigorous procedures.

How are compounded drugs regulated?

Compounding pharmacies are regulated under different frameworks depending on their classification. There are two main categories: 503A and 503B facilities, named after the relevant sections of the Federal Food, Drug, and Cosmetic Act.

• 503A Pharmacies: These are traditional compounding pharmacies that prepare patient-specific prescriptions in response to individual needs. They are regulated primarily by state boards of pharmacy and must adhere to U.S. Pharmacopeial (USP) Convention guidelines. While USP standards are robust, they are less comprehensive than those applied to 503B outsourcing facilities.
• 503B Outsourcing Facilities: These facilities, which include large-scale compounders like Olympia Pharmacy and Revelation Pharma, operate under much stricter regulatory requirements. They must comply with Current Good Manufacturing Practices (cGMP), a set of guidelines enforced by the U.S. FDA that are also applied to traditional pharmaceutical manufacturers. cGMP standards ensure that these facilities adhere to strict production, testing, and quality assurance processes similar to those used in large pharmaceutical plants.

"Part of being a 503B means being held to a higher standard than a traditional compounding pharmacy. While compounding pharmacies typically follow USP practices, 503Bs adhere to cGMP, the same standards used by large pharmaceutical manufacturers. By adhering to cGMP, this establishes a gold standard for regulatory excellence," explained Mikhael.

Are compounded GLP-1 drugs safe?

The safety of compounded GLP-1 drugs depends heavily on the source of the API and the compounding process itself. Critics have raised a key concern about the availability of authentic APIs, given that both of the major manufacturers, Novo Nordisk and Eli Lilly, have stated they do not supply or sell these ingredients to compounders.

As a result, compounding pharmacies are left to source their raw ingredients from contract manufacturers, who are often overseas suppliers.

This extended supply chain highlights the importance of transparency and quality assurance in compounding. For a compounded GLP-1 drug to be safe, it must be made using high-quality, FDA-registered APIs and undergo rigorous testing to confirm its potency and purity.

"At Revelation Pharma facilities, APIs are only from FDA-registered suppliers, ensuring that the ingredients are of the highest quality," Hodges responded. "A certificate of analysis accompanies each batch to verify its composition."

Testing and validation

The safety and efficacy of compounded medications rely heavily on the rigor of testing procedures. For GLP-1 antagonists, compounding facilities must conduct a series of quality control tests -- including sterility, endotoxin, and potency testing -- to ensure that the final product is safe for patient use. These tests can take up to 14 days, a necessary precaution to detect potential contaminants that might compromise patient safety.

"Quality testing is one of the most important aspects of compounding," Mikhael emphasized. "Ensuring a completely sterile environment during the process guarantees that quality is built into the final product."

Addressing misconceptions and building trust

Despite their critical role in filling supply gaps, compounding pharmacies often face misconceptions about the safety and reliability of their products. Some of these misconceptions are fueled by a lack of understanding about the regulatory requirements and quality controls that reputable compounding pharmacies follow.

"One common misconception is that compounded medications are less reliable or lower quality than those produced by traditional pharmaceutical manufacturers, which is simply inaccurate," stated Tara Thompson, PharmD, FAPC, vice president of clinical and marketing at Revelation Pharma. "In reality, compounding pharmacies must adhere to rigorous regulatory standards and go above and beyond to ensure that the products meet the highest quality standards."

Building trust requires transparency, patient education, and collaboration with healthcare providers. Many compounding pharmacies prioritize educating patients and providers about their safety protocols and the standards they follow, creating an informed community that understands and trusts the process.

The future of compounded GLP-1 drugs

With the increasing demand for GLP-1 drugs, compounding pharmacies are becoming essential in facilitating patient access. Advances in automation, AI and quality assurance are expected to bolster the safety and dependability of compounded medications, setting higher standards within the industry.

"Technological advancements, particularly in AI and automation, are making significant strides in the compounding sector," Hodges stated. "These innovations will enhance production efficiency, minimize errors, and help us address the rising need for personalized medications."

Ultimately, ensuring the safety of compounded GLP-1 drugs hinges on strict adherence to regulatory standards, transparency in sourcing, and a commitment to continuous improvement. With these elements in place, compounded medications can be a safe and effective alternative for patients who need them, offering a lifeline during shortages and a path forward for personalized medicine.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.