In an open letter last week, Eli Lilly warned that compounded versions of tirzepatide (Mounjaro, Zepbound) containing vitamin B12 could pose a potential safety risk, and urged the FDA to initiate a recall of such products, reports MedPage Today.
The company said that tests had uncovered “significant levels” of an impurity in the compounded products, which results from a chemical reaction between the GLP-1 tirzepatide and B12, often listed on product labels as methylcobalamin, hydroxocobalamin, or cyanocobalamin.
“Our discovery of this new impurity … highlights the risks to patients of haphazardly mixing untested additives with complex molecules like tirzepatide without rigorous testing, clinical trials, and FDA approval,” Lilly noted.
“People receiving tirzepatide-B12 products from compounders, telehealth companies, med-spas, or anyone else should be aware that they may be using a potentially dangerous product with unknown risks.”
The risks remain unknown, as the combination of tirzepatide and B12 has never been studied in humans. Consequently, there are no data on short-term or long-term effects in humans, the potential impact on receptor interaction, toxicity, or immune reactions. Also, compounders aren’t required to monitor or report adverse events in the same way as manufacturers of FDA-approved drugs.
The investigation, published in a preprint paper last week, tested US samples of compounded tirzepatide combined with various B12 analogues. Mass spectrometry revealed that the combined molecule is larger than standard tirzepatide, potentially disrupting the way it is absorbed, distributed, metabolised, and eliminated.
The samples also showed inconsistent potency, with some samples containing as little as 43% of the labelled dose.
By adding B12, some compounders claim to offer “personalised” versions of the drug, a move Lilly says is an attempt to circumvent an FDA order to cease mass-compounding of tirzepatide after its shortage was resolved in late 2024.
“B12 is just one of the many untested additives used in the mass production of compounded GLP-1s under the guise of ‘personalisation’,” the company said. “In reality, these products are not ‘personalised’ at all.”
Other additives identified included glycine, pyridoxine, niacinamide, and carnitine.
The FDA has consistently warned of the risks associated with compounded products due to a lack of federal oversight regarding safety, effectiveness, and quality. Lilly reported finding other “critical safety issues” in compounded tirzepatide samples, including bacterial contamination, high endotoxin levels, and other impurities.
However, Scott Brunner, CEO of the Alliance for Pharmacy Compounding (ACP), said the announcement “raises more questions than it answers”.
“It may be that Lilly has identified a real issue involving tirzepatide and B12 prepared by legitimate, state-licensed compounding pharmacies. If so, APC would take that extremely seriously,” he said in a statement.
“But at this point, Lilly has not provided enough information about the source of the samples, the handling of the drugs, or the nature and magnitude of the alleged impurity… for anyone outside the company to evaluate the claim.
“B12 is a well-studied and remarkably benign drug. We are about four years into the compounding of prescriber-authorised tirzepatide and B12, and there’s no alarming trend of patient adverse events associated with the compounded drug,” he added.
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