Lilly warns of impurities in compounded tirzepatide containing B12

Eli Lilly warns that compounded versions of tirzepatide -- the active ingredient in Mounjaro and Zepbound -- mixed with vitamin B12 have been found to form impurities that could pose safety risks, the pharma giant said today.

Lilly says it tested compounded tirzepatide products marketed to U.S. patients containing the additive B12 and found significant impurity levels stemming from a chemical reaction between the two substances.

"People receiving tirzepatide–B12 products from compounders, telehealth companies, medspas or anyone else should be aware that they may be using a potentially dangerous product with unknown risks," Lilly warned.

Vitamin B12, also sometimes called methylcobalamin, hydroxocobalamin or cyanocobalamin, is one of the many untested additives compounders use to mass produce compounded GLP-1s medications "under the guise of personalization," Lilly emphasized in its public warning.

The national GLP-1 drug shortages that began in early 2022 temporarily allowed compounding facilities to make copycat forms of tirzepatide and semaglutide. But years after the shortages ended, many online sellers continue to exploit legal loopholes to mass-produce "personalized" versions that contain additional additives or vitamins.

The safety of combining tirzepatide with B12 has never been studied, meaning the short and long-term effects of the impurities in humans are unknown.

The company also pointed out that compounders fall under a different regulatory framework than branded drugmakers. Traditional compounders, or 503A pharmacies, are not required to report or monitor adverse reactions related to their products, raising patient safety concerns.

Some compounders are also mixing tirzepatide with other untested additives, such as glycine, pyridoxine (vitamin B6), niacinamide (vitamin B3) and carnitine, to sidestep mass compounding restrictions, Lilly warned. The drugmaker said these additives lack proven clinical benefits for tirzepatide patients and could create additional safety risks.

The company said it has shared its findings with the FDA and has gone a step further, urging the agency to recall all compounded tirzepatide products containing these personalization additives. Lilly also advises anyone using these untested compounded products to consult their doctors about safer treatment options.

The public warning comes as people in the U.S. increasingly turn to low-cost, online knockoffs of popular weight-loss drugs, like Lilly's Zepbound and Novo Nordisk's Wegovy (semaglutide).

Earlier this month, the FDA ramped up its crackdown on misleading advertising for compounded products. The agency sent a second wave of warning letters to 30 telehealth firms over false claims made about the GLP-1 advertised on their websites. The first round of letters, sent in mid-September, targeted more than 50 telehealth and wellness companies, including telehealth company Hims & Hers.

Last month, Hims & Hers reversed course on offering a $49 compounded version of Novo's new Wegovy pill, following regulatory and legal pressure from the FDA and Novo Nordisk, and later agreed to pull back its compounded GLP-1 offerings. The telehealth company has agreed to sell Novo's branded GLP-1 medications instead, settling a patent infringement lawsuit in the process.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.