Lilly Warns of Impurities in Compounded Tirzepatide & Zepbound with Vitamin B12

Eli Lilly has issued a public warning regarding compounded versions of its medications Zepbound and Mounjaro, both containing the active ingredient tirzepatide. The pharmaceutical company’s concern centers on formulations that include added vitamin B12, which laboratory testing suggests contain significant, and currently unidentified, impurities. This development raises questions about the safety and efficacy of these compounded drugs, particularly as they are often sought as lower-cost alternatives to the brand-name medications.

Zepbound is approved by the FDA for chronic weight management and obstructive sleep apnea, while Mounjaro is approved for type 2 diabetes. Both drugs share the same active ingredient, tirzepatide, but differ in their approved uses and, insurance coverage. The issue identified by Lilly applies to compounded versions of tirzepatide, regardless of whether they are marketed for weight loss or diabetes management.

The Impurity: A Chemical Reaction

Lilly’s investigation, detailed in a preprint study funded by the company, revealed that the combination of tirzepatide and vitamin B12 leads to a chemical reaction, creating a molecule larger than tirzepatide alone. This alteration could potentially affect how the body absorbs, processes, and eliminates the drug. The study, which has not yet undergone peer review – meaning its findings haven’t been independently verified by external researchers – raises concerns because the effects of this new molecule on human health are entirely unknown.

According to Lilly, there is currently no data available regarding the short- or long-term effects of this impurity, its potential impact on the drug’s interaction with GLP-1 and GIP receptors, its toxicity, or its potential to trigger immune responses. The company has notified the U.S. Food and Drug Administration (FDA) and recommends that individuals using these compounded products consult with their physicians to discuss alternative treatment options.

Compounded Drugs and FDA Oversight

It’s crucial to understand that compounded drugs are not FDA-approved. The FDA does not review them for safety, effectiveness, or quality. Compounding pharmacies are permitted to create customized medications when a patient has specific medical needs that cannot be met by commercially available drugs – for example, requiring a different dosage or the inclusion of vitamins. However, this practice carries inherent risks.

The rise in compounded GLP-1 medications initially occurred during shortages of brand-name drugs like Zepbound and Mounjaro. While those shortages have largely been resolved, some compounding pharmacies continue to offer these medications, often by adding vitamins or other ingredients and marketing them as personalized formulations. This practice exploits a legal loophole, but introduces uncertainty regarding the drug’s composition and safety.

Why Add Vitamin B12?

Some compounders add vitamin B12, also known as cobalamin, to GLP-1 medications with the claim that it may help address fatigue, particularly in individuals with a vitamin deficiency. Vitamin B12 plays a vital role in red blood cell formation and energy metabolism. The theory is that correcting a B12 deficiency could improve energy levels and support lifestyle changes associated with weight loss. However, there is currently no scientific evidence to support the claim that adding B12 to tirzepatide injection is safe or enhances weight loss outcomes.

while rare, excessive intake of vitamin B12 can lead to toxicity, causing symptoms such as headaches, nausea, diarrhea, vomiting, and flushing, according to Dr. Yuval Pinto, an obesity and family medicine doctor at Johns Hopkins Medicine in Baltimore.

Inconsistent Potency and Quality Concerns

Beyond the impurity issue, Lilly’s testing also revealed inconsistencies in the potency of compounded tirzepatide samples. Some samples contained as little as 43% of the drug amount listed on the label. This variability raises further concerns about the reliability and effectiveness of these compounded medications.

The Compounding Pharmacy Perspective

The Alliance for Pharmacy Compounding (APC), a trade group representing compounding pharmacies, has responded to Lilly’s announcement by stating that it raises “more questions than answers.” Scott Brunner, CEO of the APC, noted that the report lacks key details needed to evaluate the claim and that there has been no alarming trend of adverse events associated with compounded Zepbound and B12 over the past four years.

Brunner also questioned the source of the samples used in Lilly’s testing, suggesting that drugs obtained from unlicensed websites or medical spas may not adhere to the same quality standards as those prepared by state-licensed compounding pharmacies. He emphasized that a med spa is not a pharmacy and that legitimate compounding pharmacies operate under strict regulations.

What Should Patients Do?

For individuals currently using compounded GLP-1 medications containing vitamin B12, experts recommend discussing alternative treatment options with their healthcare provider. If affordability or insurance coverage is a barrier to accessing brand-name medications, exploring options for coverage of GLP-1s prescribed for conditions like obstructive sleep apnea or type 2 diabetes may be worthwhile. Dr. Jorge Moreno, an obesity medicine doctor at Yale Medicine, also notes that the price gap between compounded and brand-name medications has narrowed in some cases, making the latter a more accessible option.

Ongoing Evaluation and Future Steps

The FDA is currently reviewing the data provided by Eli Lilly regarding the impurities found in compounded tirzepatide products. It is likely that the agency will issue further guidance to healthcare professionals and patients as more information becomes available. The agency’s ongoing surveillance of the compounding market will also be crucial in identifying and addressing potential safety concerns. Patients should remain vigilant and report any adverse effects experienced while using compounded medications to their healthcare provider and the FDA’s MedWatch program. MedWatch allows consumers and healthcare professionals to report serious problems they suspect are related to drugs.

The situation underscores the importance of obtaining medications from reputable sources and discussing the risks and benefits of all treatment options with a qualified healthcare professional. While compounded medications can play a valuable role in certain circumstances, they are not without risk, and careful consideration should be given to the potential consequences before using them.