I first met Jane (not her real name, of course) on a Friday afternoon in our clinic. She was referred for further evaluation of her chest pain, which, in the context of her family history of early-onset heart attacks and her morbid obesity, understandably concerned her primary care doctor.
In the exam room, we dissected her symptoms and decided we’d investigate them further with a stress test. We also discussed her weight. It was clear from our conversation that Jane was motivated. For months, she had closely watched what she ate. She took walks during her lunch break in an office park and regularly went to the gym. She tried stress relaxation techniques like meditation. She made sure that she got enough sleep.
But her efforts didn’t seem to work. She had heard about Ozempic and how it could help people like her lose weight, while also promoting her heart health. She asked me if it was a good idea to try, and I thought it was. Her insurance company, however, thought it knew better.
Recently, I’ve seen a lot of patients like Jane: Grappling with obesity and the metabolic diseases cascading from it, they are now among the plurality of Americans who have an FDA indication for semaglutide (the generic name for Ozempic). Actually obtaining this drug is no easy feat. Some patients, like Jane, have their prescriptions blocked by insurers, scared away by its price tag, through tools like prior authorization (requiring tasks like seeing a specialist in obesity medicine first, or undertaking a weight management program for months before a GLP-1 receptor agonist is on the table). Others have trouble filling their prescriptions, thwarted by drug shortages. Many can’t afford the copay.
In this environment of bureaucracy and rejection, another option has emerged: compounded semaglutide.
Compounded drugs — copycat versions of a drug made in state-licensed pharmacies, rather than by drug manufacturers — have long been used in medicine, such as to create custom medications for patients who might have specific allergies, or who need a medication that isn’t commercially available. The FDA, through its 503B program, authorizes compounding pharmacies to make non-generic drugs that are listed in shortage, such as semaglutide currently.
At first, I was cautiously hopeful. Compounded semaglutide has proven to be cheaper and more accessible than its brand-name counterpart. Many of the large direct-to-consumer companies selling them, like Ro Health and Hims, are household names, publicly traded on the New York Stock Exchange and servicing thousands of patient-consumers, providing prescriptions to treat conditions like depression, smoking cessation, and hair loss. With programs like health coaching, these companies also seem to be taking a more holistic approach to weight loss. It seemed like an attractive and easy solution to a frustrating problem.
But watching this space evolve, I’ve grown more skeptical. Compounded semaglutide, for one, isn’t user-intuitive, requiring patients to draw up doses in vials rather than use pre-filled pens. It’s no surprise then, that poison control centers have reported receiving thousands of calls related to semaglutide overdoses over the past year, up over 1,500% in volume since 2019.
Over this same period, the FDA has issued warnings about compounded semaglutide. It has received reports of adverse events affecting hundreds of patients, and cautioned that the compounded medicines themselves may be using semaglutide salts or could be adulterated with toxins or impurities. Direct-to-consumer companies, in multiple instances documented by journalists, have been quick to dispense compounded semaglutide, with little verification of information or interactions with a physician. And compounded drugs, especially when produced en masse and in pharmacies with little or no FDA oversight, are also prone to both dosing errors and sterility issues. More than 10 years ago, a compounding pharmacy in Massachusetts produced contaminated steroid spinal injections, in bulk, that resulted in a widespread fungal meningitis outbreak, injuring more than 700 patients and killing 100.
Since these drugs have emerged as compelling therapies for weight loss, the market for semaglutide has ultimately failed. Compounded semaglutide, ubiquitous online, has certainly stepped into the void to make this therapy more accessible to the general public. But in the process, it has created an ill-defined public health crisis under our noses, fed by greed and preying on vulnerable patients who turn to questionable yet convenient solutions online.
For regulators, this issue has been difficult to address. The 503B program effectively creates a loophole for direct-to-consumer health companies to sell compounded semaglutide. These pharmacies are ultimately regulated by state pharmacy boards, rather than centrally with the FDA. It is also increasingly apparent that this issue is not going away anytime soon. Compounded semaglutide has proven to be lucrative for companies like Hims, whose stock price has soared over 30% since announcing its weight loss program. In August, Hims announced it was purchasing its own 503B-compliant outsourcing pharmacy to internalize its production of compounded semaglutide, further digging its heels into the market.
Some have warned that, once semaglutide is no longer in shortage (which may be in a matter of days), the compounded semaglutide market would no longer be legally viable and would face an onslaught of lawsuits from Novo Nordisk, semaglutide’s manufacturer. But if compounding pharmacies were to make something like semaglutide (such as semaglutide mixed with vitamin B12), it could create a legal standoff between them and Novo Nordisk that could last for years, or much longer.
In the exam room, Jane and I ultimately decided to try an older medication, metformin, for now to help with weight loss alongside other lifestyle changes. I recommended against trying compounded semaglutide. For now, it carries far too many potential dangers in the way it is currently dispensed, and the patients who use it are left entirely vulnerable to the unregulated standards of the pharmacies who make them.
But going forward, I hope we can create better solutions for patients like her. Some countries, such as Australia, have taken drastic measures and have banned compounded semaglutide altogether. Given the size of the market, however, that doesn’t seem feasible at this point in the U.S. Since compounded semaglutide is likely here to stay, legislation is sorely needed to regulate its production and sale for consumer protection.
And to ultimately address the issue, we may need more creative solutions. It may involve Medicare negotiating the price for semaglutide with Novo Nordisk, or having insurers pay for it using a subscription model, similar to what was done for hepatitis C treatments when they were first released. It could even mean buying out the patent for semaglutide from Novo Nordisk, or buying out the drug company altogether.
If the status quo continues, the system of haves and have nots we’ve created in the era of Ozempic will only get worse.
Vishal Khetpal is a fellow in cardiovascular disease in the Brown University Cardiology Fellowship Program. The views expressed are those of the author and do not necessarily reflect the views of his employers.
