The Compounding Problems of Semaglutide, the Miracle Weight-Loss Drug

Semaglutide weight loss drugs are quite literally saving people’s lives. There are so many health benefits to losing weight that demand for the drugs is off the charts. Demand is so high that the manufacturer can’t keep up and the drugs are in short supply.

Where there is money to be made, there will be people willing to step in. Enter compounding pharmacies, who are catering to the demand by creating supposed duplicates of the drug.

But not all semaglutide is created equally, and concerns are rising that some pharmacies are creating inferior versions of the drug that are, at best, less effective or, at worst, dangerous.

How does semaglutide work?

Ozempic was approved by the U.S. Food and Drug Administration (FDA) in 2017 for use in adults with type 2 diabetes. After patients reported significant weight loss, Novo Nordisk rebranded the drug as Wegovy and received FDA approval in 2021 for use in chronic weight management in adults.

Semaglutide, the active ingredient for both drugs, mimics the function of a hormone that is naturally produced in the body. This hormone, released into the blood after you eat, helps lower blood sugar by stimulating insulin production, decreasing the amount of glycogen created in the liver, and ultimately making you feel fuller longer.

In short supply

These drugs work really, really well. So well, in fact, physicians prescribe Ozempic, the diabetes drug, “off-label” for weight loss. The manufacturer cannot make them fast enough due to a shortage of semaglutide. Both Ozempic and Wegovy have been on the FDA shortage list since March 2022.

This creates an attractive opportunity for compounding pharmacies. As long as the drugs stay on the official shortage list, they can be copied by compounders without fear of patent infringement.

And copy them they do. But how well?

Base or salt?

Ozempic and Wegovy use the base form of semaglutide. The base form has been approved by the FDA for the treatment of diabetes and obesity. But some compounding pharmacies are using different forms of semaglutide, known as semaglutide “salts,” that are chemically different from the base version.

Semaglutide salts have not been approved by the FDA, leading some authorities to caution patients about the efficacy or safety of the variant.

The FDA has received adverse reports from some patients after using the compounded semaglutide, which prompted them to send a public letter to the National Association of Boards of Pharmacy expressing agency concerns with the use of the salt forms of the compounded products. Some state pharmacy boards have also voiced concern.

The manufacturer of the brand-named drugs is making waves, too, and in some cases, threatening and filing lawsuits against pharmacies compounding the drugs and the health care providers administering them.

Best practices

Although the manufacturer is trying to step up production, the demand for semaglutide products will likely continue to outstrip the supply for the foreseeable future. Undoubtedly, many patients and their providers will turn to compounded variants to meet demand.

A physician’s responsibility goes beyond just prescribing the drug. They should understand how the drug is compounded and investigate the efficacy and safety of the salt forms of the product. Then decide if the salt form is appropriate for their patients.

If it is, providers should inform their patients. The Texas Medical Board considers the administration of non-FDA-approved drugs to be a form of alternative medicine. Medical board rules require that patients be informed that the drug is not FDA-approved and be told of the risks associated with the drug.

Pharmacies, too, play a key role as the backbone of our medication dispensing infrastructure. They should stay abreast of the regulations governing the compounding of semaglutide and the ethical considerations of preparing a medication for an individual patient.

They should follow the United States Pharmacopeia (USP) standards. Maintain a clean and safe environment, train personnel, appropriately label the medications, accurately identify the active ingredients, and provide accurate use instructions.

Patients have a responsibility, too. Talk to your doctor and discuss the risks and benefits of the compounded drug. If you and your doctor decide the drug is right for you, keep the lines of communication open with your physician and disclose any adverse reactions as soon as possible.

The future

The demand for these weight loss drugs will remain high for the foreseeable future. Until supply catches up with demand, growing pains will be felt in all corners of our healthcare delivery system.

From the companies that manufacture and compound the drugs to the physicians who prescribe them, the patients who take them, to the insurers who will be asked to pay for them – everyone has a responsible role to play.