What to know about cheaper, imitation weight-loss drugs

The pitch is all over social media and irresistible for many people desperate to lose weight: Get an imitation version of pricey, hard-to-find drugs like Ozempic or Mounjaro for a fraction of the cost.

But the booming business of off-brand versions of the blockbuster drugs, which trigger the hormone GLP-1 and curb hunger, has left many consumers wondering whether it is worth trying. Here’s what you should know.

What’s the difference between branded drugs and cheap imitations sold online?

Novo Nordisk, which makes Ozempic and Wegovy (active ingredient: semaglutide), and Eli Lilly, which makes Mounjaro and Zepbound (tirzepatide), went through the FDA’s rigorous process to win regulatory approval for these GLP-1 drugs, which includes studying how safe and effective they are and inspecting the manufacturing facilities. The FDA hasn’t approved any generic versions.

However, the two drugmakers haven’t been able to keep up with the seemingly bottomless demand for their products, leading the FDA to officially declare their drugs as being in shortage. That designation has opened the door for specialized compounding pharmacies to churn out copies of the blockbuster drugs, which they are legally permitted to do when FDA-approved drugs are in shortage and they meet certain requirements. Compounded GLP-1 drugs require a prescription.

What are compounding pharmacies and why are their GLP-1 drugs cheaper?

Compounding pharmacies traditionally customize a prescription medication to suit an individual patient’s needs, such as by mixing up a liquid formulation for someone who can’t swallow pills. They are licensed and inspected by state regulators. The FDA exercises some oversight over their practices but doesn’t approve their products.

When it comes to weight-loss medications, pharmacies have much lower overhead costs than Novo Nordisk and Eli Lilly, which spent billions of dollars to research and develop the drugs and meet FDA’s exacting quality standards.

For their raw ingredients, compounding pharmacies turn to contract manufacturers - largely overseas - which have registered with the FDA as makers of semaglutide and tirzepatide. Converting the raw active ingredient from powder form to an injectable solution doesn’t take advanced chemistry, pharmacists say, enabling pharmacies to offer GLP-1 drugs to health-care providers for a couple hundred dollars a month or less.

Some research suggests that the brand manufacturers, meanwhile, are substantially marking up the price for profit. A Yale University-led study earlier this year found injectable semaglutide could be profitably made for less than $5 a month, compared with Ozempic’s list price of $968.52 for a month’s supply. Novo Nordisk said in a statement that the study didn’t take into account its costs for research and development or those of building “first-in-the-world manufacturing facilities.”

Are compounded weight-loss drugs safe?

With a diffuse supply chain and multiple vendors engaged in making a sterile, injectable medication, there is some additional safety risk of pharmacy-made drugs. How much is hotly debated.

The FDA says that compounded medications in general are not as safe as drugs that have been exhaustively reviewed by the agency. Between August 2021 and mid-July, it has reviewed 288 reports of patients having bad reactions to compounded semaglutide and 108 such reports for tirzepatide, a spokesperson said. Those are tiny fractions of the tens of thousands of adverse-event reports people have submitted for all types of the drugs, including the brand-name versions, which have well-documented side effects.

Novo Nordisk and Eli Lilly have argued in lawsuits and public statements that compounded GLP-1 drugs are unsafe, saying their own testing has found impurities in compounded versions of their medications.

“The proliferation of entities claiming to offer compounded tirzepatide is a safety issue,” Lilly said in a statement, adding that such products lack FDA approval and haven’t been shown to be safe or effective. Novo Nordisk cited purity deficiencies in compounded semaglutide from six pharmacies it has sued, saying they could jeopardize patient safety.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said the companies’ allegations are unproven. “Look, FDA-approved drugs should always be the first-line drug therapy,” he said. Because the drugmakers can’t meet the demand for their products, pharmacies are “saving the day” by stepping in to fill the void, Brunner added.

Andrew Kraftson, director of the weight navigation program at University of Michigan, said patients ask him about compounded semaglutide, but he won’t prescribe it.

“There’s just a lot of unanswered questions,” Kraftson said. “People are just injecting it into their bodies with a lot of trust and a lot of hope.”

What can I do to minimize risk with compounded GLP-1 medications?

For those inclined to pursue compounded GLP-1 drugs despite the risks, here are a few things to consider:

-Identify the health-care provider who would prescribe it. That will allow you to examine the provider’s experience and look up their regulatory history in the state where they are licensed.

-Check which compounding pharmacy the prescriber or service uses, then search the websites of the state pharmacy board or the FDA to see if regulators have taken disciplinary action.

-Ask the provider or the compounding pharmacy for a certificate of analysis that shows the results of testing the raw ingredients.

=Some websites in the past have sold “semaglutide sodium.” The FDA doesn’t consider semaglutide sodium to be the same ingredient in approved drugs like Ozempic and Wegovy. Instead, it has said the sodium version shouldn’t be used to make copies of the drugs in shortage and has “not been shown to be safe and effective.”

What is it like to take a compounded injectable GLP-1 drug?

For any version of the drugs, the process begins by visiting - in person or online - a health-care professional, who writes a prescription and orders the medication.

Telehealth firms prescribing compounded drugs often have the drug shipped to a patient’s home, where it typically comes in a vial with a syringe, in contrast to the brand-name versions that come in pre-filled injection pens.

Jess Winfrey, 36, who has polycystic ovary syndrome and lives in Dallas, began taking compounded semaglutide and later tirzepatide last October because she didn’t think her insurance would cover the medications to help her lose weight. Winfrey said she’s received prescriptions from three telehealth firms - in one case after filling out a questionnaire without talking to a health-care provider.

Before trying compounded GLP-1 medications, Winfrey had never given herself a shot before. “It took me 30 minutes because I kept pulling the medication out into the syringe and pushing it back in, because I didn’t know if I did it right,” she said. “By the end of it, I had sweat beads on my forehead because I was so nervous.”

But Winfrey said she quickly got over her fear. Now a paid promoter of the weight-loss drugs, she live-streams her “injection days” on TikTok to help others overcome their anxiety.

How long will the FDA designation allowing for compounded GLP-1 drugs last?

Demand is so great that the shortages are expected to last into next year, but even executives at Novo Nordisk and Eli Lilly are reluctant to give firm predictions. The FDA says it will resolve a shortage when the manufacturer can meet “total national historical demand,” and the agency has verified it has additional “safety stock” and that all back orders have been filled.

Eric Tichy, who manages the pharmaceutical supply chain at Mayo Clinic in Rochester, Minn., said injectable GLP-1 drugs are the “number one back-ordered medications” for the hospital system but that the shortage has improved significantly in the last six months.

The FDA’s database shows limited availability for two doses of Mounjaro and Zepbound, and for the three lowest doses of Wegovy. Eli Lilly said that it is on track to boost production of its tirzepatide-based drugs in the second half of this year, though its executives have said the shortages could persist into next year. Novo Nordisk said it can’t speculate when all doses of Wegovy will be fully available.

Will cheap compounded GLP-1 drugs go away once the shortage is resolved?

Compounding pharmacies that make exact copies of FDA-approved GLP-1 drugs will have to stop when they are no longer in shortage. That means some people who pay a few hundred dollars a month may be looking at a large increase in cost for the brand-name injections.

Still, Hims and Hers, a publicly traded telehealth firm, is betting it will be able to sell compounded GLP-1 drugs for the foreseeable future, although analysts are not so sure.

“The company’s ability to sell semaglutide once the shortage ends remains uncertain,” Michael Cherny, a Leerink Partners analyst, wrote in a June research note. Hims and Hers did not directly address its plans once the shortages end.

There may be other ways to keep compounded drugs on the market once shortages are over. For instance, many compounding pharmacies add vitamin B-12 to a compounded GLP-1 drug. If that made a therapeutic difference for patients, a pharmacy could argue that it’s more than a copy of a brand-name drug, said Robin Feldman, a professor at the University of California College of the Law in San Francisco and an expert on pharmaceutical law.

“However, GLP-1 drugs are the new gold rush,” she said. “In unexplored territory, one should be cautious in making predictions.”

Novo Nordisk’s patent for semaglutide expires in 2032, while Eli Lilly’s patent for tirzepatide expires in 2036. The companies hold other patents on the drugs as well, and it could take even longer for generic versions to make it to market.