Lilly Says Compounded Tirzepatide With Added Vitamin B12 Contains Impurities. Is It Safe?

Note: Compounded drugs are not approved by the U.S. Food and Drug Administration (FDA) and may carry greater risks than FDA-approved treatments.

Pharmaceutical company Eli Lilly has issued a new warning about copycat compounded versions of its blockbuster GLP-1 tirzepatide drugs Mounjaro and Zepbound, claiming that variations with added vitamin B12 contain “significant” impurities.

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The findings come from a preprint study funded by Lilly that has not yet been peer reviewed, meaning the results haven’t been independently evaluated by outside researchers for publication in a medical journal.

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In a statement, Lilly said that it has “notified the U.S. Food and Drug Administration (FDA) about these findings and recommends that people using these untested products contact their physicians for advice and discussion on alternative treatment options.”

The Study Identified a Chemical Reaction Between Tirzeptide and Vitamin B12

Lilly’s laboratory testing found that the interaction between tirzepatide and vitamin B12 produced a molecule larger than tirzepatide alone — a change that could theoretically affect how the drug is absorbed, distributed, metabolized, or eliminated in the body, the study authors wrote.

According to the Lilly statement, this discovery is concerning because nothing is known about the short- or long-term effects of this molecule in humans, or whether there are any potential impacts on the drug’s efficacy, toxicity, or immune reactions.

Tirzepatide has never been studied in combination with B12, Lilly said, and the compounders making these combination drugs are not required to monitor or report negative reactions in patients, known as “adverse events.”

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The study also reported inconsistent potency among the compounded tirzepatide samples, with some containing as little as 43 percent of the drug amount listed on the label.

While it’s unclear whether the finding poses any real risk to patients, the study authors conclude that “the identification of widespread impurity adds to the existing quality concerns presented by compounded tirzepatide.”

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Compounded GLP-1s Are Not FDA-Approved

Jorge Moreno, MD, an assistant professor and obesity medicine doctor at Yale Medicine in New Haven, Connecticut, says the findings highlight a broader concern that obesity specialists have about compounded versions of GLP-1 medications.

Drugs like Zepbound and Mounjaro that are approved by the FDA have undergone a lengthy process to ensure they are safe and effective. Compounded medications, which are not FDA-approved, do not undergo the same rigorous vetting.

With a copycat drug, “If the recipe isn’t followed the same way as the FDA-approved medication, we simply don’t know if it’s safe or effective because the recipe has changed,” Dr. Moreno says.

Compounders have not shared any data on the new molecule produced from the interaction of tirzepatide and vitamin B12, “so we don’t know what its safety profile is or whether it could affect how well the medication works,” Moreno says.

Furthermore, although it’s very rare, getting too much vitamin B12 can lead to toxicity, says Yuval Pinto, MD, an obesity and family medicine doctor at Johns Hopkins Medicine in Baltimore. “I have seen a case of that in our clinic. Megadoses of B12 can lead to headaches, nausea, diarrhea, vomiting, and flushing,” he says.

Why Add B12 to a Compounded GLP-1?Compounded versions of GLP-1 medications became widely available during shortages of brand-name drugs, when the FDA permitted their production. But now that the drugs are no longer in short supply, compounders can no longer legally make copycats, and the FDA is cracking down on the dupes.

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Some compounders have created workarounds to continue offering lower-cost versions of GLP-1s by adding vitamins or other ingredients and marketing the mixtures as personalized formulations — a legal loophole.

Vitamin B12, also called cobalamin, is a nutrient involved in red blood cell formation and energy metabolism. Some compounders claim adding B12 to a GLP-1 may help address fatigue, particularly in people with a vitamin deficiency. In theory, correcting low B12 levels could improve energy and help people maintain lifestyle changes that support weight loss.

But there isn’t evidence that adding B12 directly to tirzepatide injection is safe or improves weight loss outcomes.

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Other additives identified in compounded GLP-1 samples included glycine, niacinamide, pyridoxine, and carnitine — combinations which also have not been vetted for safety or efficacy.

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Compounding Group Says Lilly’s Announcement Raises ‘More Questions Than Answers’

Leaders in the compounding pharmacy community say Lilly’s announcement lacks key details needed to evaluate the claim.

In a statement, Scott Brunner, CEO of the Alliance for Pharmacy Compounding (APC), called the report concerning but incomplete. The APC is a nonprofit industry trade group representing compound pharmacies nationwide.

“We are about four years into the compounding of prescriber-authorized Zepbound and B12, and there’s no alarming trend of patient-adverse events associated with the compounded drug,” Brunner said.

Brunner also questioned where Lilly obtained the samples used in its testing, noting that drugs sold by unlicensed websites or medical spas may not meet the same standards as those prepared by state-licensed compounding pharmacies. “A med spa is not a pharmacy,” he said.

If Lilly has identified a real issue involving tirzepatide plus B12 prepared by legitimate, state-licensed compounding pharmacies, APC would take that extremely seriously — but more information needs to be shared for scientists outside Lilly to evaluate the claim, said Brunner.

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What Should You Do if You’re Taking Compounded Zepbound With Vitamin B12?

For people currently using compounded GLP-1 medications, experts recommend talking with your healthcare provider about alternatives.

If affordability or insurance coverage for weight loss is an issue, you may qualify for a GLP-1 with another condition such as obstructive sleep apnea or type 2 diabetes, says Moreno.

In some cases, the price gap between compounded and brand-name medications has also narrowed, Moreno says.

“Out-of-pocket options for the branded medication have lowered in cost and can sometimes be less expensive than compounded options,” he says.