Only one in four U.S. patients prescribed Novo Nordisk’s Wegovy or Ozempic for weight loss were still taking the popular medications two years later, according to an analysis of U.S. pharmacy claims provided to Reuters that also showed a steady decline in use over time.

The analysis does not include details about why patients quit. But it does offer a longer view on the real-world experiences of patients taking the drugs than previous research that studied use over a year or less.

Evidence that many people may stop using the weight-loss therapies not long after starting is influencing a debate over their cost to patients, employers and government health plans.

Wegovy and similar medicines, which belong to a class of drugs known as GLP-1 receptor agonists, can cost more than $1,000 per month, and may require extended use to yield meaningful benefits.

Their U.S. prices have drawn fire recently from President Joe Biden and other public officials, who said such drugs could cost the country $411 billion per year if only half of adults with obesity used them. That is $5 billion more than Americans spent on all prescription drugs in 2022.

“GLP-1s for all isn’t cost effective,” said Dr. Rekha Kumar, an obesity specialist at New York Presbyterian-Weill Cornell Medical Center and chief medical officer at Found, an online weight-loss program. “People want to provide obesity care to their employees, but they want to do it in a way that doesn’t bankrupt them.”

Prime Therapeutics and Magellan Rx Management, a pharmacy benefits manager, reviewed pharmacy and medical claims data for 3,364 people with commercial health plans that cover GLP-1 drugs. They had all received new prescriptions between January and December 2021, and had a diagnosis of obesity or a body mass index of 30 or higher.

The PBM excluded patients using the drugs for type 2 diabetes, for which these medicines were originally developed. The mean age of patients included in the analysis was 46.5 and 81% were female.

Last year, Prime published data that found 32% of patients were still taking a GLP-1 medicine for weight loss 12 months after their initial prescription. The new data shows that overall, for all the drugs included in the study, only about 15% were still on their medication after two years.

For Wegovy, 24.1% of patients persisted with therapy over two years without a gap of 60 days or more, down from 36% who had stayed on the drug for a full year. With Ozempic, which has the same active ingredient as Wegovy – semaglutide – 22.2% of patients kept filling their prescriptions at two years, down from 47.1% who had used it for one year.

Older GLP-1 drugs fared worse. At two years, only 7.4% of patients were still taking Novo’s Saxenda, a less effective weight-loss drug that some health plans require patients try before newer GLPs like Wegovy or Eli Lilly’s Zepbound.

In the analysis, 45% of patients were taking Ozempic or Wegovy. Others were taking Saxenda or Victoza, which are both liraglutide, Rybelsus, an oral version of semaglutide, or Lilly’s Trulicity (dulaglutide).

The analysis also found that 26% of patients switched GLP-1 drugs during therapy, perhaps reflecting shortages or changes in insurance coverage, according to Dr. Patrick Gleason, assistant vice president for health outcomes at Prime/MRx and a co-author of the analysis.

Both Novo and Lilly have been unable to keep up with unprecedented demand for the new medicines.

Novo Nordisk in a statement cited several limitations to the analysis. It noted that Wegovy wasn’t launched until June 2021, the middle of the study period, and wasn’t immediately covered by insurance. And Ozempic isn’t approved for weight loss, which can affect patients’ coverage and persistence with therapy, the Danish drugmaker said.

The company said it “does not believe these data are sufficient to draw conclusions about overall patient adherence and persistence to various GLP-1 medicines, including our treatments.”

The newer GLP-1s in clinical trials helped people lose more than 15% of their body weight by suppressing appetite and promoting a feeling of fullness. They are being tested for a host of other health benefits that could improve insurance coverage.

Wegovy in March won U.S. approval for reducing the risk of strokes and heart attacks in overweight and obese adults.

The analysis didn’t track long-term use of Lilly’s Mounjaro and Zepbound, which launched after the study’s starting point. Eli Lilly declined to comment on the overall findings.

Prime/MRx did not ask patients why their prescriptions stopped. Gleason said it’s likely a mix of side effects such as nausea and vomiting, out-of-pocket costs not covered by insurance and supply shortages.

Some patients may decide to stop the medication after successfully losing weight, doctors said. Other studies have shown that most patients who quit their GLP-1 drugs usually regain most of the weight.

“No one really knows how long you should be on these medications,” said Dr. Walid Gellad, a professor of medicine at the University of Pittsburgh who studies medication adherence.

Some clinics and telehealth services aren’t screening patients properly or providing adequate coaching on nutrition and exercise alongside the drug, Kumar said, leading to poor results and patients giving up.

Prime/MRx is owned by 19 U.S. Blue Cross and Blue Shield health insurance plans and manages pharmacy benefits for about 38 million people.

Dr. David Lassen, the PBM’s chief clinical officer, called the steady drop in persistence two years into therapy concerning.

“It’s not leveling off but getting slightly worse,” he said. “It’s really about sustainability of weight loss in order to achieve long-term outcomes.”