GLP-1s often contain untested additive combinations, study finds

by Sophia Friesen, University of Utah Health Sciences

edited by Gaby Clark, reviewed by Robert Egan

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Use of GLP-1 receptor agonist medications (GLP-1s) has skyrocketed in recent years, and many people are using "compounded" GLP-1 products: medicines that include GLP-1s as well as other active substances, some of which are not regulated by the FDA. A new study found that compounded GLP-1s now make up a large majority of weight-loss medicines, commonly containing vitamin B12 analogs that have not been tested for safety in combination with GLP-1s.

"Compounded GLP-1s have grown into a large market, but because nearly all of it is cash-pay, it is essentially invisible to the insurance claims data researchers typically use," says Joey Mattingly, Pharm.D., Ph.D., associate professor of pharmacotherapy, vice chair of research for the University of Utah College of Pharmacy and the first author on a study describing the results. "We had no systematic picture of what is actually being dispensed to patients."

The new study, published in JAMA, aimed to change that. Using data from Nebraska, which has an unusually comprehensive prescription tracking database, the study analyzed the number of compounded GLP-1 prescriptions filled across the state. Prescriptions spiked from zero in 2018 to 86% of all compounded weight-loss prescriptions in 2025.

Some of the most common additives were vitamin B12 analogs, such as cyanocobalamin, and levocarnitine, a molecule involved in metabolism. These additives are often marketed as preventing side effects associated with GLP-1s, but there is little evidence that they are effective, and the drug combinations have not been tested for safety.

Mattingly emphasizes that compounded GLP-1s may behave differently from the approved standard. "Compounded products with additives are not the same as the FDA-approved drugs, and the composition and quality of what a patient is injecting are often unverifiable," he says. "The risks are largely unknown."

The results show an urgent need for better safety monitoring of compounded products, the authors say—including both improved tracking of compounded medicines and better safety standards.

Meanwhile, Mattingly says that doctors should be vigilant about compounded products. "Ask patients specifically about compounded GLP-1 use," he suggests. "Many are obtaining these products online, paying cash, and that will not appear in medication histories drawn from claims or pharmacy records."

Publication details

T. Joseph Mattingly et al., Compounded GLP-1 Dispensing Patterns and Vitamin B 12 Coformulation, JAMA (2026). DOI: 10.1001/jama.2026.21223

Journal information: Journal of the American Medical Association

Key medical concepts

L Carnitine

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Clinical pharmacologyWeight managementEndocrinology Provided by University of Utah Health Sciences Who's behind this story?

Gaby Clark

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