Weight-loss drugs are supposed to be forever … until they run out

Maez Waibel lost more than 30 pounds in nine months on the new weight-loss drugs, sparking a substantial improvement in health. But instead of feeling happy and relieved, Waibel’s days have been freighted with a different emotion: anxiety.

Waibel went through two months’ worth of Wegovy before Waibel’s pharmacy ran out. All the CVS, Walgreens and Wegmans stores within a few hours’ drive from Waibel’s home in Downingtown, Pa., were out, too.

So Waibel went without for three months while the weight piled back on. Waibel was finally able to locate a stash of medication again in January. It was a lower dose than Waibel needed. But it was better than nothing.

“You get to the point where you think, ‘Is this going to be my life?’ ” Waibel, 29, said.

Ozempic and Mounjaro, used to treat diabetes, and their respective counterparts for weight loss, Wegovy and Zepbound, were approved by the Food and Drug Administration as “forever” drugs that are supposed to be taken in perpetuity.

But circumstances have not cooperated. Recurrent shortages, shifting insurance coverage, patient whims and a lack of longer-term guidance about side effects and dosing have forced doctors and patients to make up as they go what quantity of drugs to take and when. It amounts to a human experiment of trial and error.

Some patients are starting, stopping and switching weight-loss medications based on what’s in stock, or stretching out doses far past the recommended weekly cycle, or stopping cold turkey when they can’t find supply. And, in some cases, they simply run out of cash for injections that can cost roughly $1,000 a month without insurance.

The shortages have come in waves since last fall. They highlight weaknesses in America’s health care system and raise questions about the government’s responsibility in ensuring access to critical drugs and drugmakers’ prioritization of the weight-loss market when they cannot meet the needs of diabetes patients for whom the drugs were initially designed.

Complex supply chain

The erratic supply has also exposed lack of coverage by insurers or their rigidity about reimbursing for the medications.

Mounjaro, Ozempic and Zepbound were available in all dosages last week, but shortages of Novo Nordisk’s Wegovy persist, according to an FDA update in August. Indianapolis-based Eli Lilly and Co., which makes Mounjaro and Zepbound, and Novo Nordisk, the manufacturer of Ozempic in addition to Wegovy, have cited skyrocketing demand for the supply crunch and said they are working to ramp up production.

Novo Nordisk said total weekly prescriptions for Wegovy have more than doubled since January and that it will “continue to manage shipments” of the lowest, starting dose to focus on ensuring sufficient supply for patients already on the medications.

“We have made significant progress improving Wegovy supply while maintaining a clear focus on supporting patients who require care to start and stay on this medicine,” the company said in a statement.

Eli Lilly cautioned that while availability is sufficient nationally for its drugs, the “supply chain is complex, especially for refrigerated medicines, and there may be many reasons a particular pharmacy does not have a particular dose of the medicine in stock.”

The American Pharmacists Association, which represents about 45,000 pharmacists, said increased production has yet to make much difference in availability for many consumers. Brigid Groves, vice president for professional affairs for the organization, said members still grapple with huge backlogs and shortages.

“We are hopeful that at some point supply will be replenished, but right now it is still hit or miss as far as what patients can get on a regular basis,” Groves said last week.

The Senate has been investigating the high prices of the Novo Nordisk drugs and held a hearing Tuesday on the topic. Sen. Bernie Sanders (I-Vt.), chair of the Senate health committee, questioned why Ozempic is priced at $969 a month in the United States but $155 in Canada and $59 in Germany. (Many U.S. patients pay less out of pocket because of manufacturer coupons.) A study by Yale University researchers published in March estimated that the production cost of a one-month supply of Ozempic is 89 cents to $4.73.

“The issue that we’re discussing today is so important it impacts every aspect of our health-care system, the federal budget, private insurance,” Sanders said in his opening statement.

Novo Nordisk said the net price of Ozempic has declined by 40 percent since its launch in the United States, and Wegovy “is following a similar trajectory.”

“We appreciate that it is frustrating that each country has its own healthcare system but making isolated and limited comparisons ignores this fundamental fact,” the company said in advance of the hearing.

Diana Thiara, medical director of the University of California at San Francisco Weight Management Clinic, called the shortages “horrible” and said drugmakers drove up demand through direct-to-consumer advertising but then could not meet demand, creating a chaotic and precarious situation for patients.

“It’s hard to start new patients on drugs when there’s no supply,” Thiara said, adding that even those patients who are able to begin treatment get whiplash from repeatedly switching drugs due to shortages.

The situation is so confusing that physicians report that some patients simply give up. Thiara said one patient with obesity recently told doctors, “I can’t continue this cat and mouse game” of searching for the medication every few weeks and opted for bariatric surgery, a major treatment shown to be effective in controlling obesity for years but that carries significant risk.

The chaos in the market is exacerbated by patients using medications on an as-needed basis or playing around with dosages when their weight plateaus or when on vacation or during holidays, when they do not want the injections potentially limiting enjoyment of food. In other cases, patients stop taking the drugs because of side effects.

As a result, Emory Healthcare physician Mohammed Ali said he has mixed feelings about the runaway success of the medications—which belong to a class called GLP-1—for weight loss. While he is pleased that the drugs work well in reducing patients’ weight, he cautioned that other medications were adopted quickly and found years later to have dangerous side effects such as heart failure, and he worries that the variable ways patients use GLP-1 medications make it even more difficult to spot issues that arise.

“There’s a whole area of science that needs to happen but hasn’t happened,” Ali said.

A drug for life

The idea behind the compound used in the drugs is that it mimics something naturally produced in the body that makes people feel less hungry and more full and that lowers blood sugar. Drugmakers have marketed them as medications that should be taken regularly for life, akin to the cholesterol-lowering statin drugs or blood pressure pills.

But recent analyses show a large number of people are not taking the drugs long term.

A report published in May by Blue Cross Blue Shield Association found that more than 30 percent of patients tracked under the health plan dropped out of treatment after the first four weeks.

Prime Therapeutics/Magellan Rx Management, a pharmacy benefits manager, reported last year that claims data showed only 32 percent of people taking GLP-1 drugs for weight loss were on them a year later. A follow-up study, first reported by Reuters in July, found that number dropped further after two years—to about 15 percent. The report also noted that about a quarter of patients switched GLP-1 drugs during their treatment, which study authors suggested might be related to shortages or insurance coverage.

The low adherence rates raise questions about the effectiveness of treatment (doctors typically recommend at least 12 weeks of therapy to see benefit) and unequal access (the Blue Cross data showed that the lowest sustained use was among patients who were most likely to face barriers because of cost, transportation and language).

“Right now, a lot of the people who are able to be on the medications are the privileged people who can afford them or have insurance for them. There’s not enough emphasis on equity,” said Melanie R. Jay, co-director of the NYU Langone Comprehensive Program on Obesity.

Off-ramps and holidays

The question of how to help patients manage shorter-term use and going off the medications sparks vibrant debate among obesity doctors.

Jay said she prefers a slower titration downward rather than stopping the treatment completely. If a patient is on 2.4 milligrams of a GLP-1 drug, she might put them on 1 mg to see if they can maintain their weight.

“Then if you find yourself struggling and gaining weight, my advice would be, do you want to go back up?” Jay said.

Andrea D. Coviello, head of the UNC Health weight management clinic in North Carolina, said changing medication schedules usually comes up when patients reach their targets—with a healthy weight or diabetes in remission or blood pressure in a normal range. She does not recommend stopping or titrating down.

As a result, only a small minority of her patients have gone off the drugs and most, within a year or year and a half, regained the weight they’d lost, and other health issues returned, she said.

“It makes no sense to get on the drugs if the point is to stop,” Coviello said.

David E. Cummings, a professor of medicine at the University of Washington, said that in recent months, some researchers have begun mobilizing to study intermittent use of the drugs—one month using the drug as indicated, then one month without any medication, for instance.

“It’s not just important for patients but for the medical system because these drugs are so darn expensive,” Cummings said.

He said the cost to the patient or medical system for two years of continuous use of the drugs would pay for gastric bypass surgery, which is permanent. With up to one-third of Americans suffering from obesity, he said, it’s unclear how the health-care system could bear such costs.

“The financial consequences are staggering,” Cummings said.

A key study used in securing FDA approval for Wegovy as a lifetime medication for weight loss was based on patients using the drug continuously for about a year and 4 months and then stopping. It found that about two-thirds regained the weight they lost. A similarly designed study had comparable results for tirzepatide (Zepbound).

Shorter on-off intervals were not studied.

“It does raise the question, ‘Could we gain some mileage on short holidays?’ That’s unexplored terrain, and it remains a possibility,” Cummings said.

It will probably be years before such studies are completed and, meanwhile, many patients continue to be stuck hunting for medications on occasion.

Waibel has been on a 2.4 mg maintenance dose of Wegovy since June and found a steady supply through a local pharmacy, but a friend who is just starting out has had difficulty getting any form of GLP-1 filled in recent weeks.

“Some pharmacies, whether brick and mortar or online, will tell you directly that they can’t guarantee a refill because they reserve a supply for those already receiving the medication,” Waibel said.

Brian Castrucci, a 50-year-old from Rockville, Maryland, who has type 2 diabetes, suffered a heart attack amid challenges controlling his blood sugar. He tried Ozempic, but that made him extremely nauseous. His doctor prescribed Trulicity, but it was out of stock.

So he moved on to Mounjaro, which worked well the week he was on it, but then he was unable to fill his prescription earlier this year. He sought help from his endocrinologist—who has a concierge practice that takes fewer patients, allowing more attention—and an office staffer spent hours calling pharmacies within driving distance from the D.C. region. The search was a success. There was a three-month supply about an hour away from Castrucci’s home, and he immediately took off work and drove there.

“You’re finding what’s left on the market,” Castrucci said. “The challenge here is like everything—that one’s own personal privilege can dictate access.”

He feels lucky to have the medication for at least another few months, but angry for others not as fortunate: “You are at the mercy of a nameless, faceless company. Nothing provides a more acute feeling of helplessness.”