How Are Endos Handling Weight-Loss Drug Shortages?

Once again, in the face of the ongoing shortage of anti-obesity medicines (AOMs), the US Food and Drug Administration (FDA) has warned against using compounded versions of the drugs, reinforcing its previous position and that of expert obesity organizations.

The Alliance for Pharmacy Compounding continues to argue that the compounded weight-loss drugs are legitimate options, claiming that FDA Commissioner Robert Califf conflated compounded drugs and counterfeit substances.

While heeding the need to be cautious, endocrinologists and other obesity/diabetes specialists are taking matters into their own hands. Here is what they told Medscape Medical News about how they are handling the shortage.

Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine specialist at Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts, is adamant. “I emphatically disagree with the use of compounded agents, even amid shortages, secondary to inadequate testing and safety concerns,” she said. “I have my patients wait…Otherwise, they can use the LillyDirect™ option.”

Amy E. Rothberg, MD, DABOM, director of the Weight Management Program & Rewind at the University of Michigan, Ann Arbor, Michigan, said, “Given uncertainty about potency, other additives/ingredients/fillers/preservatives and/or contaminants, most of my endo colleagues do not endorse the use of compounded drugs.”

“We are being creative. We have switched patients to the drug that is available — ie, from Zepbound or Wegovy to Saxenda,” she said. “We will sometimes use a lower dose, if available, and use one of the other first-generation AOMs with the GLP-1. Or, we will entirely change to a first-generation AOM to stem the tide until a GLP-1 becomes available.”

Furthermore, she noted, some patients stretch out their weekly dose to every 10 days.

“We are also intensifying our efforts around lifestyle and behavior change and having regularly scheduled check-ins with dietitians and physicians, and we have patients enroll in a comprehensive weight management program.”

Ivania Rizo, MD, DABOM, spokesperson for The Obesity Society and director of Obesity Medicine at Boston Medical Center, Boston, Massachusetts, said the shortages “have created incredible frustration for patients and providers. Providers like myself have to send many messages to our prior authorization and pharmacy teams to see what alternatives are covered by insurance and are available at the pharmacy.”

“At times we have to decrease the dose, as this is the only dose available, or we may need to switch to other GLP-1s, which then requires the patient to learn to use a new medication and see if they tolerate it,” she said. “The shortages cause significant work for providers and patients, as we all try to find pharmacies that have the dose needed or alternatives.”

Joshua Joseph, MD, MPH, an endowed professor at The Ohio State University Wexner Medical Center in Columbus, Ohio, said, “In my practice, we have been navigating the shortage by working with patients to find pharmacies that have available medication with mixed success.”

Michael A. Weintraub, MD, of NYU Langone Health Diabetes & Endocrine Associates in New York City, commented, “The risks of compounded GLP-1 RAs outweigh the possible benefits. If a pharmacy does not have a particular GLP-1 RA dose, they may have other doses in stock.”

A different dose should not be much higher than the one the patient has been taking, or it could trigger gastrointestinal side effects, and not much lower, or it might cause weight regain, he noted.

“For example, if a patient is taking Zepbound 7.5 mg but that dose is out of stock, we can fill the 10-mg or 5-mg dose,” he said. “Alternatively, patients can call neighboring pharmacies or mail-order pharmacies, or we can switch from one GLP-1 RA to another at a comparable dose, if needed.”

“If a patient discontinued a weekly GLP-1RA for more than 2 weeks, they should restart at a low dose,” he cautioned. “Restarting at the same dose can trigger severe gastrointestinal side effects.”

Jaime Almandoz, MD, an associate professor in UT Southwestern Medical Center’s Division of Endocrinology and associate professor of medicine and medical director of the Weight Wellness Program in Dallas, Texas, observed, “Many compounding pharmacies are promoting products like ‘generic’ semaglutide or tirzepatide when no such thing exists. The patents for these medications are still in place, and these medications have a very complex manufacturing process, so it is not clear where compounding pharmacies are sourcing them.”

“The statements from regulators and our professional societies should make prescribers concerned for the medicolegal ramifications of using untested compounded formulations, especially if a medical misadventure were to occur,” he added.

“For now, if incretin therapies are not available due to supply or are not covered by insurance, we consider using non-incretin AOMs that are approved, safe, and effective for treating obesity. Some of these older medications — for example, phentermine and topiramate — are available in generic forms, which make them much more affordable, regardless of insurance coverage…We should partner with our patients to use alternative approved therapies.”

Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, commented, “It is important for patients to obtain prescriptions only through state-licensed pharmacies.” Given that there are other effective AOMs on the market, he advises that providers continue to work with patients to identify alternative treatment solutions until the shortage is resolved.

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the Keck School of Medicine of the University of Southern California, Los Angeles, California, commented, “I would say that there are legitimate compounding pharmacies that provide safe forms of semaglutide/tirzepatide, such as Henry Meds. But others are selling products that are not the active drug. People need to be very careful where they are getting their compounded medications from, especially online.”

What the Manufacturers Say

Lilly, the manufacturer of tirzepatide (Mounjaro, Zepbound) and dulaglutide (Trulicity), and Novo Nordisk, the manufacturer of semaglutide (Ozempic, Wegovy) and liraglutide (Saxenda), acknowledge that the AOM shortages are frustrating for providers and patients and say they are working to boost supply and availability.

“We are enabling more new US patients to initiate treatment by more than doubling the amount of the lower-dose strengths of Wegovy into the US market [as of January 2024] while gradually increasing overall supply throughout the rest of the year,” Allison Schneider, director, media relations & issues management, at Novo Nordisk, told Medscape Medical News. “However, it’s important to be aware that overall demand will continue to exceed supply, which means that some patients may still have difficulty filling Wegovy prescriptions.”

Regarding Saxenda, she said that although the company is continuing to produce the drug, “We expect shipment delays to US wholesalers throughout 2024, which will result in many patients continuing to have difficulty filling their Saxenda prescriptions.”

A spokesperson for Lilly told Medscape Medical News that the company anticipates intermittent backorders on certain doses of Mounjaro and Trulicity.

“We recognize this situation may cause a disruption in people’s treatment regimens, and we are moving with urgency to address it. We are in ongoing contact with the FDA to provide timely updates. For additional supply updates, please visit the FDA’s website linked here.”

All doses of Zepbound are available for pharmacies across the United States to order from their wholesaler, she added.

The following experts declared relationships with industry: Stanford has received funds from Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, Novo Nordisk, and Empros Pharma; Joseph is a board member for Buckeye Health Plan; Almandoz serves on advisory boards for Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Kushner is on the medical advisory board for Novo Nordisk. The other experts declared no relevant relationships.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.