Hundreds of thousands of Americans stand to soon lose their access to cheaper weight-loss drugs, with a federal crackdown on copycat versions threatening to disrupt treatment and raise costs.

The Food and Drug Administration has ordered producers and sellers of the less expensive products to wind down operations in the coming weeks now that it has declared there are no longer shortages of the blockbuster drugs Wegovy and Zepbound.

Produced through a process of mixing drug ingredients known as compounding, the copycat medications had spawned a booming multi-billion-dollar industry. Patients turned to compounding because their health insurance would not pay for the brand-name drugs and they could buy the compounded versions for less than $200 a month in some cases.

Eli Lilly and Novo Nordisk now offer the brand-name drugs for $500 a month in most cases to patients who pay with their own money instead of going through insurance. Until recently, patients sometimes had to pay over $1,300 a month.

The F.D.A. ordered compounding for versions of Eli Lilly’s Zepbound to end last month. Small compounders have until April 22 to stop making and selling versions of Novo Nordisk’s Wegovy; large compounders have until May 22.

It is not clear how the F.D.A. will enforce these deadlines. The Health and Human Services Department, which oversees the F.D.A., declined to answer questions for this article.

Robert F. Kennedy Jr., the health secretary, has criticized the weight-loss medications, saying that people would be better off eating healthy food, though he said last week that they were “extraordinary drugs.” He has not weighed in on the cheaper copycats.

The compounding industry has been waging a public-relations campaign and fighting in court to reverse the orders, but has been unsuccessful so far. Although the market for compounded weight-loss drugs is expected to shrink under federal scrutiny, it’s unlikely to dry up altogether. Some providers plan to keep offering the drugs at dosages that aren’t standard or by mixing in vitamins, moves they hope will allow them to skirt the crackdown.

“We’re about to see just how creative the compounding industry can get,” said Lindsay Allen, a health economist at Northwestern University.

If these strategies keep compounding going even at a reduced scale, it could siphon billions of dollars of business away from Novo Nordisk and Eli Lilly. Drugmakers view these tactics as an illegal attempt to bypass their patents.

In a long-overlooked corner of pharmacy, compounding obesity drugs has generated huge business for telehealth companies and medical spas that connect patients with prescribers. One of the largest providers, the telemedicine company Hims & Hers, reported over $225 million in revenue from a category of weight-loss drug offerings that analysts said primarily represented compounded versions of Wegovy.

Compounders have supplied not only patients with obesity, but also those with diabetes who couldn’t find the brand-name drugs because of the shortages.

A trade group for large compounders estimates that millions of patients are getting the weight-loss drugs through compounding, which, if accurate, would rival sales of the brand-name products. No one is tracking the specific number of patients getting the drugs this way.

With the F.D.A.’s deadlines, people who can no longer afford the drugs and stop taking them face the prospect of regaining weight and reversing progress in combating other health issues.

In Woodbury, N.Y., one pharmacy, Town Total Compounding Center, has been supplying the drugs for about 400 patients, charging as little as $210 for a month’s supply. To comply with the F.D.A.’s deadlines, it recently stopped selling versions of Eli Lilly’s product and plans to soon discontinue selling versions of Novo Nordisk’s product.

“We have a lot of patients very concerned that they’re about to get cut off,” Joseph Navarra, the pharmacist and owner, said.

In Jefferson Township, N.J., Victoria Weyand, 66, paid $200 a month for compounded drugs for obesity that were produced by her local pharmacy. She is on Medicare, which generally will not pay for Wegovy or Zepbound. The Trump administration recently rejected a Biden proposal that would have expanded Medicare coverage of those drugs for millions of people.

Ms. Weyand said she had lost about 25 pounds since starting the drugs last November. But she ran out of her supply of the compounded version of Zepbound earlier this month, and her pharmacy stopped offering it to comply with the F.D.A.’s order. She said she mainly relies on Social Security, and won’t be able to afford the extra $300 a month to switch to the brand-name drug.

“I don’t know what I’m going to do now. I’m very upset. I feel lost,” Ms. Weyand said. “I just pray something changes.”

Compounders and their supporters say the F.D.A. acted too soon when it declared the shortages over, because many patients are still having trouble finding the drugs at pharmacies. They caution that ending compounding will worsen supply issues. They also warn that desperate patients who can’t afford the brand-name drugs will instead seek out potentially dangerous counterfeit drugs online.

Seeking to protect their market share, Novo Nordisk and Eli Lilly have been filing lawsuits against providers and sending cease-and-desist letters. Novo Nordisk’s chief executive, Lars Fruergaard Jorgensen, recently said that compounding was hurting his company’s sales.The drugmakers and other critics have also been raising doubts about the safety and quality of the compounded products, which are often made with active ingredients imported from China.

“We have been conducting a reckless national experiment with compounded new weight-loss drugs,” Dr. David Kessler, a former F.D.A. commissioner, said at a congressional hearing last week.

Behind a booming business

Before the arrival of mass-produced pharmaceuticals, most medications were compounded by a pharmacist. More recently, compounders have stepped in amid shortages of chemotherapy drugs and the antibiotic amoxicillin. They routinely tailor-make medicines for people who have allergies or trouble swallowing.

“Compounding was never intended to compete with the drugmakers,” said Scott Brunner, the chief executive of a trade group for compounders.

But the Ozempic era brought compounders more patients, revenue and attention than ever before. The big business emerged in 2022, when the F.D.A. first declared Novo Nordisk and Eli Lilly’s drugs in shortage. Federal law allows compounding when there’s a supply shortage or when a patient’s needs can’t be met by drugs through the usual channels.

Compounded products are produced differently from the brand-name drugs. Novo Nordisk makes its drug in-house. Eli Lilly has been doing most of its manufacturing itself, though in recent years it has also relied on contractors, including in China.

American compounders typically buy the drug’s active ingredient as a powder from a supplier, often in China. They say they test for quality and purity. They mix in salt, sterile water and chemicals to control acidity levels.

Some compounders then dispense the drugs directly to patients, while others provide a supply through telemedicine websites or medical spas.

Compounded drugs do not go through the F.D.A.’s approval process, nor are they tested in clinical trials that might detect safety problems.

The F.D.A. regulates compounding, though less rigorously than it does drugs that go through its review. Compounders are supposed to source their active ingredient from suppliers that are registered with the agency. The F.D.A. or state pharmacy officials inspect compounding operations.

Compounders say they follow strict production standards and that their products are safe and effective. But the F.D.A. says that compounded drugs “pose a higher risk to patients” than those that it approves.

The F.D.A. has issued warnings to several compounders, including for not properly sterilizing their weight-loss products. Some compounders have also sold the drugs in forms that are not permitted by the F.D.A.

The F.D.A. office that monitors compounding, a small unit staffed with chemists, pharmacists and other experts, has been largely spared from mass layoffs at the agency. But experts say oversight has been lax, even as weight-loss drug compounding has exploded, because regulators have long had insufficient staff and funding to police compounding violations.

A rush before the deadlines

The Biden administration was still in charge when the F.D.A. set deadlines to end compounding versions of Zepbound. The Trump administration had taken over by the time the F.D.A. decided to halt compounding of Wegovy alternatives.

Dr. Marty Makary, the new F.D.A. commissioner, had not been appointed when the agency imposed the deadlines. Until late last year, Dr. Makary was an executive at Sesame, a telehealth company offering a compounded version of Wegovy. (The company said it plans to discontinue the offering soon.) Dr. Makary pledged before his confirmation to divest his stock options in Sesame, which is a privately held company.

Some providers have been rushing to eke out sales ahead of the regulatory deadlines. “Stock Up Before the FDA Clamps Down!” one telehealth company, Priority Meds, said in a recent Facebook advertisement. “We’ll send you a six month supply before the FDA regulations take place!”

Some providers argue that because compounding is permitted when a patient has a need that can’t be met through drugs already on the market, they can keep offering what they call “personalized” versions of the weight-loss drugs even after the F.D.A. deadlines. Experts said that compounding to address particular patient issues was never intended for mass sales and represented a murky legal area.

Hims & Hers said it planned to keep offering compounded versions of Wegovy at doses that are not available from Novo Nordisk.

Empower Pharmacy, a large compounder, said it intended to continue offering versions of the drugs that are mixed with B vitamins. Empower pitches the combination as a way to relieve side effects like nausea or otherwise benefit the patient. Eli Lilly recently sued Empower over the tactic.

Some providers are also mounting a public-relations campaign to try to sway regulators and lawmakers to allow compounding to continue.

Hims & Hers has been collecting signatures and sending them to the F.D.A. and members of Congress.

And Sean Spicer, a former press secretary for President Trump, has been on a media tour warning that ending compounding will harm patients. He said he was hired by Ivim Health, a telemedicine company where he is also a patient.

Mr. Spicer said he turned to compounding after spending months trying unsuccessfully to get the drugs through his insurance. He said he recently got a six-month supply of a compounded version of Eli Lilly’s drug, right ahead of when Ivim stopped offering it to comply with the F.D.A.’s order. The Wall Street Journal first reported Ivim’s hiring of Mr. Spicer.

“I don’t think people have fully recognized what this decision is going to do,” Mr. Spicer said. “My hope is that the Trump administration reviews it before they get stuck with the consequences.”