The Changing Landscape of GLP-1 Medications

By Tracey Truitt, Shareholder, Sandberg Phoenix

Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized the treatment landscape for type 2 diabetes and obesity. These medications were first approved for the treatment of type 2 diabetes back in 2005.  Since then, new formulations have been introduced, patents have been filed, and the market for them has exploded.  Zepbound, Monjauro, Ozempic, and Wegovy have become household names and while many famous people have denied taking them for their weight loss benefits, it is estimated that 12% of the adult population in the US has taken at least one of these drugs.  It is no wonder, the active ingredients of these brand name drugs, including semaglutide and tirzepatide, have shown significant efficacy in managing blood glucose levels and promoting weight loss. However, the rapid rise in their popularity has also resulted in several issues, ranging from regulatory challenges and legal battles to safety concerns and market dynamics.

At the center of most of these issues, the FDA has played a pivotal role in regulating the availability and compounding of GLP-1 drugs. In 2022, the FDA declared a shortage of these drugs, which opened the door for drug compounders to make compounded versions of them.  As the supply of these medications stabilizes, the FDA has updated its enforcement discretion policies. For instance, the FDA announced that it would not take action against compounders for violations related to tirzepatide and semaglutide until specific dates this year, depending on the type of compounding facility. This temporary leniency was granted to avoid disrupting patient treatment during shortages. However, as the shortages resolve, the FDA is tightening its regulations, which could limit the availability of compounded versions of these drugs.

In another battle to retain and extend exclusivity for this lucrative market, Eli Lilly has filed a lawsuit against the FDA, challenging the classification of its GLP-1 drug, retatrutide, as a drug rather than a biological product. The classification hinges on the definition of amino acids, with significant implications for compounding regulations. If retatrutide is classified as a biologic, it would not be eligible for compounding under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FDCA). This legal battle underscores the complexities and high stakes involved in the regulatory landscape of GLP-1 drugs.

The FDA has also looked into the safety of compounded GLP-1 drugs. Compounded drugs do not undergo the same rigorous review for safety, effectiveness, and quality as FDA-approved drugs. This lack of oversight can lead to various issues, including dosing errors and the use of unapproved ingredients. For example, the FDA has received reports of adverse events related to compounded semaglutide and tirzepatide, some of which required hospitalization. These adverse events were often linked to dosing errors or the use of salt forms of semaglutide, which are not approved for compounding.  The FDA has also identified the presence of counterfeit and illegally marketed versions of GLP-1 drugs, such as Ozempic. These counterfeit drugs can contain incorrect or harmful ingredients, posing significant risks to patients. The agency has issued warning letters and taken action against companies selling these unapproved drugs, but the problem persists, highlighting the need for vigilance among consumers and healthcare providers.

The FDA’s recent actions to remove semaglutide and tirzepatide from its drug shortage list have significant implications for the availability of compounded GLP-1 drugs. This move effectively cuts off the primary legal route that allowed compounders to produce these medications. As a result, several telehealth companies, such as Hims & Hers and Ro, have announced that they will no longer offer certain compounded GLP-1s.  While the removal of these drugs from the shortage list suggests that brand-name options should be more readily available, their high prices—often exceeding $1,000 per month without insurance—make them inaccessible for many. Although manufacturers like Eli Lilly and Novo Nordisk have introduced direct-pay programs to reduce costs, compounded versions generally remain more affordable, typically costing around $200 per month. The potential loss of these lower-cost options could exacerbate access issues for patients.

The patent landscape for GLP-1 drugs, particularly semaglutide, is another changing area. In China, for example, the patent for Ozempic is set to expire in 2026, 6 years sooner than in the U.S., opening the market to biosimilar developers. This impending patent expiration has led to increased competition, with several companies vying to enter the market. The introduction of biosimilars could potentially lower costs and increase accessibility, but it also raises questions about the quality and efficacy of these alternatives compared to the original brand-name drugs.

The issues surrounding GLP-1 drugs are complex and multifaceted, involving regulatory challenges, safety concerns, market dynamics, and legal battles. While these medications offer significant benefits for managing type 2 diabetes and obesity, the rapid rise in their popularity has highlighted several areas that require careful oversight and regulation. As the FDA continues to refine its policies and as legal battles unfold, the landscape for GLP-1 drugs will likely continue to evolve, with significant implications for patients, healthcare providers, and the pharmaceutical industry.