Eli Lilly warns of potential safety risks after detecting an unknown impurity formed when compounded tirzepatide is mixed with vitamin B12. The company alerted the FDA and raised concerns over untested additives used in compounded GLP-1 drugs.
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company has issued a public warning about potential safety risks linked to compounded tirzepatide products that are mixed with vitamin B12, after internal testing identified a previously uncharacterized impurity formed through a chemical reaction between the two compounds.
According to the company, laboratory testing of compounded products marketed in the United States that combine tirzepatide with B12 including forms such as methylcobalamin, hydroxocobalamin, or cyanocobalamin revealed significant levels of an impurity created when the molecules interact.
The safety profile of this impurity remains unknown, including its potential toxicity, immunogenicity, pharmacokinetics, and effects on tirzepatide’s interaction with GLP-1 and GIP receptors.
Lilly said the findings are concerning because tirzepatide has never been clinically studied in combination with vitamin B12. As a result, there is no evidence regarding the short- or long-term health effects of such formulations in humans.
The company also noted that many compounded drug manufacturers are not required to systematically monitor or report adverse events, further limiting the ability to detect potential safety signals.
Patients receiving tirzepatide-B12 compounded products from compounders, telehealth providers, or medical spas may therefore be exposed to products with unknown risks, Lilly warned.
The company said it has informed the U.S. Food and Drug Administration of its findings and recommends that patients using these compounded formulations consult their physicians about safer, approved treatment options.
Lilly reiterated its broader concerns about the proliferation of mass-compounded versions of its FDA-approved tirzepatide medicines, Mounjaro and Zepbound. The company said some sellers attempt to by-pass regulatory restrictions by marketing compounded products as “personalized” formulations that include additives such as vitamin B12. In reality, Lilly said these additives are often used uniformly across products rather than tailored to individual patient needs.
Beyond B12, Lilly reported that some compounders are also mixing tirzepatide with substances such as glycine, pyridoxine, niacinamide, and carnitine, creating new combination products that have not undergone rigorous testing or regulatory review. The company emphasized that these additives have no proven clinical benefit when combined with tirzepatide and may introduce additional safety risks.
Lilly also said it continues to detect other quality concerns in compounded tirzepatide products, including bacterial contamination, elevated endotoxin levels, and additional impurities not present in its FDA-approved medicines.
Lilly’s warning comes amid growing scrutiny of compounded GLP-1 medicines across the obesity drug market. Recently, Novo Nordisk criticized telehealth platforms promoting compounded versions of its therapies in a dispute involving Hims & Hers Health, highlighting growing tensions between drug manufacturers and companies distributing compounded weight-loss drugs.
At the same time, the U.S. Food and Drug Administration has repeatedly warned that compounded GLP-1 products may carry higher risks because they are not reviewed for safety, effectiveness, or manufacturing quality, and has recently stepped-up enforcement actions against the mass distribution of compounded tirzepatide and similar medicines.
The company welcomed recent regulatory steps aimed at curbing the mass distribution of compounded anti-obesity drugs and urged regulators to take further action to protect patients. Lilly also called on authorities to consider recalls of compounded tirzepatide products that contain untested additives such as vitamin B12.
Overall, the discovery of the new impurity underscores the risks associated with combining complex biologically active molecules like tirzepatide with other substances without rigorous testing, clinical trials, and regulatory oversight, the company said.
Reference
An open letter from Eli Lilly and Company warning of potential patient safety risks associated with tirzepatide compounded with vitamin B12, 12 March 2026, An open letter from Eli Lilly and Company warning of potential patient safety risks associated with tirzepatide compounded with vitamin B12 | Eli Lilly and Company
About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.
