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