JAMA: Compounded GLP-1s Carry B12 or Levocarnitine, Paid in Cash

What the JAMA research letter did

On October 22, 2026, JAMA published online the research letter "Compounded GLP-1 Dispensing Patterns and Vitamin B12 Coformulation" by T. Joseph Mattingly II, Emeka Elvis Duru, Matthew L. Maciejewski and Rena M. Conti, of the University of Utah, Duke and Boston University². The authors used comprehensive Nebraska prescription drug monitoring program (PDMP) data to describe compounded weight-loss prescriptions, and the ingredients in compounded GLP-1s².

The article's introduction sets the scene: compounded GLP-1 receptor agonists expanded rapidly in the US, driven by marketing, manufacturer shortages and lower out-of-pocket costs². The full text with results sits behind a paywall, so here we cite only the figures the University of Utah itself published¹².

What the additives are, and what is unknown

The University of Utah says the additives are marketed as reducing GLP-1 side effects, but there is little evidence they work and the combinations have not been tested for safety¹. The lead author put it plainly: "The risks are largely unknown." He also said: "We had no systematic picture of what is actually being dispensed to patients"¹.

A separate University of Colorado Anschutz study in JAMA Health Forum (July 17, 2026) found the same pattern from the supply side: among 75 weight-loss clinics and med spas in Oklahoma and West Virginia, 92% offered compounded semaglutide and nearly 87% offered compounded tirzepatide, and more than half reported formulations combined with B vitamins³⁴⁵. Lead author Michael DiStefano said, "For many of these added ingredients, we simply don't have good evidence showing they improve safety or effectiveness"³. That study did not evaluate the safety or quality of the products³⁴.

Why FDA scrutinizes add-ins

On April 1, 2026, FDA clarified that it intends to treat a compounded product as an "essentially a copy" when it has the same active ingredient as a commercial drug at a similar strength and the same route; its example was semaglutide plus vitamin B12 (cyanocobalamin) within 10% of commercial strengths⁷. A law-firm analysis read that example as a signal that many semaglutide-plus-additive products may fall in that category absent strong individualized clinical justification⁹.

The warning letter to Empower Pharmacy (September 18, 2026) applied that logic: it cited tirzepatide/niacinamide and semaglutide/cyanocobalamin products that "appear to be essentially copies" of approved drugs⁸. We covered it in our article on the Empower letter. FDA also states that it does not review compounded drugs for safety, effectiveness or quality before they are marketed⁶.

Quality: the tirzepatide-B12 impurity

In March 2026, Eli Lilly publicly warned that its testing found "significant levels of an impurity" from a chemical reaction between vitamin B12 and tirzepatide¹⁰. Lilly's team later published the methods in Expert Opinion on Drug Safety: they described a widespread, previously unidentified impurity in compounded tirzepatide-B12 products, with unknown clinical effects¹¹. The authors are Lilly employees, which readers should weigh, and the samples are not representative of every product on the market.

Pharmacovigilance data point the same way without being conclusive: an analysis of FDA's adverse event reporting system (FAERS) found higher reporting odds of preparation errors, contamination and hospitalization for compounded versus non-compounded products, with the caveat that voluntary reports cannot prove causation¹². Other work has described administration errors with compounded semaglutide at a poison control center and quality problems in semaglutide sold online¹³¹⁴.

Cash payment: the visibility gap

The practical lesson is visibility. The University of Utah explains that many compounded purchases are paid in cash and so do not appear in insurance claims data; Mattingly advises clinicians to "ask patients specifically about compounded GLP-1 use"¹. The authors call for better safety monitoring and stronger standards for compounded medicines¹.

For the physician, the medication history may be incomplete on two fronts: what the patient bought on their own, and what exactly is in the vial. FDA itself had received 990 adverse event reports for compounded semaglutide and more than 730 for compounded tirzepatide as of May 31, 2026, and says underreporting is likely⁶. The market is shifting too: see our article on Hims & Hers and Lilly.