Note: Compounded drugs are not approved by the U.S. Food and Drug Administration (FDA) and may carry greater risks than FDA-approved treatments.
The pharmaceutical company Eli Lilly has issued a caution regarding imitation compounded versions of its popular GLP-1 tirzepatide medications, Mounjaro and Zepbound. They claim that the versions which include added vitamin B12 contain “significant” impurities.
The warning stems from a preliminary study funded by Lilly that has not yet undergone peer review. Consequently, these results have not been validated by external researchers for publishing in medical journals.
In their statement, Lilly mentioned that they have “notified the U.S. Food and Drug Administration (FDA) about these findings and recommends that individuals using these unverified products consult their healthcare providers for advice regarding alternative treatment options.”
A Chemical Interaction Between Tirzepatide and Vitamin B12
Lilly’s laboratory analyses revealed that the reaction between tirzepatide and vitamin B12 creates a molecule larger than tirzepatide by itself—an alteration that could potentially impact its absorption, distribution, metabolism, or elimination in the body, as noted by the study authors.
The findings worry Lilly as the effects of this new molecule on humans, both short- and long-term, remain unknown. They are also uncertain about whether it influences the medication’s effectiveness, toxicity, or immune responses.
Lilly emphasized that tirzepatide has never been clinically tested alongside vitamin B12, and the compounders producing these combination drugs are not obligated to monitor or report any negative health reactions, known as “adverse events.”
The study also found that the compounded tirzepatide samples displayed inconsistent potency, with some containing merely 43 percent of the drug quantity stated on the label.
While it’s still uncertain whether this finding truly poses risks to patients, the authors concluded that “the identification of widespread impurities enhances the existing concerns regarding the quality of compounded tirzepatide.”
Compounded GLP-1s Are Not FDA-Approved
Jorge Moreno, MD, an assistant professor specializing in obesity medicine at Yale Medicine in New Haven, Connecticut, emphasizes that these findings bring attention to a larger issue that obesity specialists have concerning compounded variants of GLP-1 medications.
Unlike Zepbound and Mounjaro, which have cleared the rigorous scrutiny of the FDA, compounded medications lack this thorough examination.
Dr. Moreno explains, “When a copycat drug is involved, if the formulation deviates from the FDA-approved version, we simply don’t have any assurance about its safety or efficacy since the formula has altered.”
Furthermore, compounders have not disclosed any information about the new molecule resulting from the tirzepatide and vitamin B12 interaction, leading to uncertainty about its safety profile and its potential effects on the medication’s performance, adds Moreno.
Additionally, although rare, excessive intake of vitamin B12 can lead to toxicity. According to Yuval Pinto, MD, an obesity and family medicine doctor at Johns Hopkins Medicine in Baltimore, “We have encountered cases of this in our clinic. High doses of B12 can result in headaches, nausea, diarrhea, vomiting, and flushing.”
Reasons for Adding B12 to a Compounded GLP-1
Compounded versions of GLP-1 drugs started to appear during shortages of brand-name medications, when the FDA permitted their production. Now that these drugs are no longer in short supply, compounders are legally barred from making imitations, prompting the FDA to tighten regulations on these alternatives.
Some compounders have developed workarounds, offering lower-cost variations of GLP-1 drugs by incorporating vitamins or other components and marketing these mixes as customized formulations—exploiting a legal loophole.
Vitamin B12, or cobalamin, is essential for the formation of red blood cells and energy metabolism. Some compounders assert that including B12 in a GLP-1 preparation may help mitigate fatigue, particularly in those with a vitamin deficiency. Theoretically, addressing low B12 levels could enhance energy levels, aiding individuals in maintaining lifestyle changes conducive to weight loss.
However, there is no evidence to support that combining B12 with tirzepatide injections is safe or enhances weight loss results.
Other substances found in compounded GLP-1 samples included glycine, niacinamide, pyridoxine, and carnitine—combinations that have not gone through any safety or efficacy evaluations.
Compounding Community Raises Concerns Over Lilly’s Announcement
Leaders within the compounding pharmacy sector have stated that Lilly’s announcement raises more questions than it answers.
Scott Brunner, CEO of the Alliance for Pharmacy Compounding (APC), described the report as worrisome but lacking crucial details necessary for a comprehensive assessment. The APC is a nonprofit group representing compounding pharmacies across the nation.
“We have been compounding prescriber-authorized Zepbound with B12 for about four years now, and there’s been no alarming trend of adverse patient reactions associated with the compounded medication,” Brunner stated.
He emphasized concerns regarding the origin of the samples used in Lilly’s testing, suggesting that pharmaceuticals obtained from unlicensed websites or medical spas might not adhere to the same standards as those from state-licensed compounding pharmacies. “A med spa cannot be equated with a pharmacy,” he remarked.
Should Lilly have valid concerns about tirzepatide combined with B12 prepared by legitimate, state-licensed compounding pharmacies, the APC would treat that matter with utmost seriousness; however, more information is imperative for scientists beyond Lilly to properly evaluate the claim, Brunner added.
Advice for Those Using Compounded Zepbound with Vitamin B12
For individuals currently taking compounded GLP-1 medications, experts advise consulting with your healthcare provider about potential alternatives.
If financial constraints or insurance coverage for weight loss medications present challenges, you might qualify for a GLP-1 medication targeting another condition, such as obstructive sleep apnea or type 2 diabetes, states Moreno.
Moreno also mentions that in some scenarios, the cost differential between compounded and brand-name medications has decreased.
“Out-of-pocket expenses for branded medications have dropped and may even be lower than some compounded alternatives,” he notes.
