The decision to prescribe a compounded or brand-name glucagon-like peptide 1 (GLP-1) medication for obesity treatment was never simple, but recent developments have complicated it further.
Both Eli Lilly and Company and Novo Nordisk have asked the US Food and Drug Administration (FDA) to place their GLP-1 medications, tirzepatide and semaglutide, on its Demonstrable Difficulties for Compounding or DDC Lists, which would prohibit compounding the medications. Lawsuits are another issue. The Outsourcing Facility Association, a trade group, filed a lawsuit against the FDA, calling on it to restore tirzepatide to the shortage list after the FDA removed it on October 2, despite pharmacies still experiencing shortages, according to the association. The FDA is reevaluating the decision and won’t take action against compounders in the interim, with a joint status report scheduled for November 21.
In the midst of the lawsuits and pending decisions, healthcare providers are taking a variety of approaches when they need to decide between compounded vs brand-name GLP-1s for obesity treatment. The Alliance for Pharmacy Compounding, another trade group, offers a number of suggestions for doctors faced with compound or brand-name decisions and has a website tool to be sure a compounding pharmacy meets standards.
According to the FDA, a drug may be compounded for a patient who can’t be treated with an FDA-approved medication, such as a patient who has an allergy to a certain ingredient and needs medication to be made without it, or for a medication that appears on the FDA Drug Shortages List.
Here’s how five healthcare providers make the decision.
Physicians Weigh in
Hard pass: “I have no experience with compounded formulations by choice,” said W. Timothy Garvey, MD, MACE, an obesity specialist and the Charles E. Butterworth, Jr, professor and university professor at the University of Alabama at Birmingham. “I think our patients deserve better.”
However, he acknowledged: “This is a difficult situation when there is a lack of access to medications patients need.” Even so, “online prescriptions [for compounded medications] are often done without an evaluation for obesity complications and related diseases and ongoing active management, making a complications-centric approach to care impossible.”
That’s not the optimal approach to treating obesity or other chronic diseases, he told Medscape Medical News.
Rather than prescribe compounded GLP-1s for weight loss, he said, other options exist. Among them: Prescribe Ozempic off-label for obesity.
“Plus, we have a good first-generation obesity medication — phentermine/topiramate — that gets close to 10% weight loss on average in clinical trials that is available and less expensive.”
Other options, he said, are to switch to lower doses of the brand name that may be available until the treatment dose needed is out of shortage status or, the less desirable option, wait for availability, which means the patient may be off the medication for a month or more.
He acknowledged none of these options solves “the problem of high costs [for brand-name drugs] and lack of insurance coverage.”
In agreement is Caroline Apovian, MD, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.
“Doctors who are obesity medicine specialists like myself in academic centers do not prescribe compounded semaglutide or tirzepatide,” she said.
Many of the compounded prescriptions, she said, come from telehealth virtual–only companies interested in profits.
Brand names preferred: “Brand-name versions as far as I’m concerned are always preferred,” said Sarah Stombaugh, MD, an obesity medicine and family medicine physician in Charlottesville, Virginia. She terms it irresponsible for a prescriber to give a patient a compounded GLP-1 if the patient has prescription coverage and the brand name is available.
Her approach: She first checks the patients’ coverage. Do they have coverage for these medications for obesity? If so, she said, she will do a prior authorization to get the brand name approved. If a brand name is available but not covered, she explores other options. One is the cash pay option for Zepbound in vials. It’s more affordable than the typical $1000 cash price for the brand name GLP-1s but still pricey, at about $400-$549 for lower doses, she said.
She looks at drug makers’ discount coupons, or whether a patient with a history of cardiovascular issues might qualify for coverage on Wegovy. Another option is to give the patient a prescription for Mounjaro or Ozempic to fill from a Canadian pharmacy for about $400 a month.
“I think a lot of people jump quickly to compounding,” she said.
She views it as a last resort and reminds other healthcare providers that the compounded medications aren’t cheap, either, typically costing $100-$500 a month depending on dosage. And, she said, “We have many who get the brand name for $25 a month [by using discount cards and insurance coverage].”
When prescribing a compounded medication is necessary, it’s important for healthcare providers to know that the quality of the compounding pharmacies varies greatly, Stombaugh said. A prescriber needs to pick the compounding pharmacy, not the patient, and needs to vet it, she said, asking about protocols it follows for sterility and for chemical analysis, for instance.
Stombaugh is hopeful that several new medications under study and now in phase 3 trials will soon provide enough competition to drive down the price of the current brand-name GLP-1s.
History of mistrust: Robert Dubin, MD, associate professor of research at the Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, Louisiana, and program director for its obesity medicine fellowship, sees a role for compounding and has for several years, but acknowledged that many in his community are against it.
He estimates that about 75% of his colleagues in the Baton Rouge area are opposed to prescribing compounded GLP-1s. He chalks it up to a “track record of distrust,” based on reports of infractions called out by the FDA for some compounding pharmacies as well as physicians not being familiar with the process.
Dubin said he will prescribe a compounded medication if the brand name isn’t available. Cost is also a consideration. “If there’s not a problem with availability and there’s not a problem with cost, then why compound?”
For anyone considering prescribing compounded GLP-1s, he said, “The first step, I believe, is having a relationship with the compounding pharmacy. If you don’t have that, it could be very difficult. We don’t want to send people to a black hole, and we aren’t sure what is going to happen.” He urges colleagues to educate themselves about compounding pharmacies.
Official shortage list vs real world: “The official shortage list doesn’t always reflect the real world,” said Amanda Guarniere, NP, a nurse practitioner with a self-pay telehealth and in-person practice and director of growth for Collaborating Docs, a service based in Arlington, Virginia, that pairs nurse practitioners with supervising physicians.
“When Zepbound and Mounjaro came off the [FDA] shortage list a few weeks ago, patients were still calling around and couldn’t find it in their county.”
It’s important to vet compounding pharmacies before dealing with them, she said.
“I have accounts with two compounding pharmacies who I trust,” she said. She’s researched their quality control provided and is comfortable with their standards. When appropriate, she said, the cost savings of compounded GLP-1s over brand name is “pretty significant,” with compounded medicine costs about 20% of brand-name costs.
When the brand name is back, how might a prescriber still write a prescription for a compounded version? “Compounded versions are typically compounded with something else,” Guarniere said.
For instance, compounded tirzepatide often includes vitamin B12 and other B vitamins, which may help with the side effect of nausea. So a prescriber might decide that the compounded prescription is more appropriate and justified because the patient would benefit from the additive, she said.
What Else to Know: Alliance Views
On November 7, the Alliance for Pharmacy Compounding, a trade group, responded to Lilly’s request to put tirzepatide on the “demonstrably difficult to compound (DDC)” list, asking the FDA to deny it. The group also took issue with criticism of compounded GLP-1s from the Novo Nordisk CEO.
The alliance offers perspective and a number of suggestions for doctors faced with compound or brand-name decisions, including using its website tool called “Is It Legit?” to be sure a compounding pharmacy meets standards.
“When these [GLP-1] drugs came out, I don’t think anybody anticipated them to be such blockbusters,” said Tenille Davis, PharmD, a board-certified sterile compounding pharmacist and chief advocacy officer for the Alliance for Pharmacy Compounding. Shortages have plagued the GLP-1s since their approvals, with Wegovy approved on June 4, 2021, and Eli Lilly’s Zepbound on November 8, 2023.
The proposed “Demonstrably Difficult to Compound (DDC)” rule, published in March 2024, aims to finalize the six criteria for a medication to land on that list, she said. No drugs are currently on this list, Davis said.
For now, she said, prescribers faced with a compound vs brand-name decision should be aware of the pending lawsuit concerning tirzepatide and that the FDA has said it will cease most enforcement action until 2 weeks after it reviews the decision to remove the medication from the shortage list and issues a new determination.
Davis suggests prescribers have conversations now with their patients about their options and to tell them it may be necessary to transition from the compounded medicines to brand name. “This may require insurance prior authorizations, so if they are going to transition from compounded tirzepatide to Zepbound and Mounjaro, it’s good to start the process sooner rather than later so there isn’t an interruption in care.”
Earlier this year, the three leading obesity organizations issued a statement, advising patients that they do not recommend the use of compounded GLP-1s.
Garvey is a consultant on advisory boards for Eli Lilly and Company, Novo Nordisk, and several other pharmaceutical companies. Apovian had no relevant disclosures. Stombaugh, Dubin, and Guarniere had no disclosures.
Doheny is a Los Angeles freelance journalist.
