Combining tirzepatide with vitamin B12, a common additive in compounded versions of the drug, yields an impurity that could alter the drug’s toxicity profile and pose safety risks to patients, the company said in an open letter.
Eli Lilly has warned the public about potential safety risks of taking compounded versions of its blockbuster weight-loss and diabetes drug tirzepatide.
In particular, the pharma found that many of these remixed formulations combine tirzepatide with vitamin B12, which can react with the active ingredient and yield an impurity, Lilly said in an open letter on Thursday. The impurity is “concerning because nothing is known about its short- or long-term effects in humans,” the company added.
There is also very little information about how the impurity might alter the way tirzepatide interacts with its target receptors, and whether it might affect the drug’s toxicity and immunogenicity. This chemical byproduct could also potentially change how tirzepatide is absorbed into, distributed throughout and cleared from the body, according to Lilly.
The 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 said.
Lilly has long fought compounding, the practice of making custom formulations of drugs to meet the individual needs of patients or to help supplement supply in the case of a shortage. In October 2024, the FDA declared the tirzepatide shortage over, removing the rationale for allowing its routine compounding. Months later, in April 2025, Lilly launched a strong legal offensive against compounders, suing four telehealth providers for promoting and selling knockoff tirzepatide.
In January, Arizona-based provider Strive Compounding Pharmacy hit back with its own lawsuit alleging that Lilly and fellow obesity leader Novo Nordisk are engaged in a “coordinated effort to suppress competition.”
Efforts of the two companies to stifle compounders, Strive’s complaint continued, is “cutting off an essential channel between patients with prescriptions for personalized medicines and the pharmacies that could fill those prescriptions.”
Lilly countered this argument in its Thursday letter. “In reality, these products are not ‘personalized’ at all,” the company wrote, adding that “untested additivies” are used “under the guise of ‘personalization’ but that their use by compounders is only seeking to “circumvent the law.” Their altered formulations create “a range of new and untested combination drugs,” according to the letter.
“These so-called ‘personalized’ compounded tirzepatide products show they may pose even greater risks to patients than previously known,” the pharma added.
Lilly has good reason to protect its tirzepatide franchise. In 2025, the drug brought in $36.51 billion across its two brands: Mounjaro for type 2 diabetes and Zepbound for chronic weight management. This sum puts Lilly’s weight loss portfolio cleanly ahead of Merck’s mega blockbuster Keytruda, a cornerstone cancer therapy, which made $31.7 billion last year.
