Four in five people taking GLP-1 medications for weight loss quit them in two years, even though the drugs are supposed to be taken much longer to maintain their benefits, according to a new report by Eagan-based Prime Therapeutics.

Wednesday's report is disappointing because many people regain all their weight after discontinuing the injectable drugs such as Wegovy and put themselves back at risk for costly chronic diseases, said Pat Gleason, an associate vice president for health outcomes at Prime, which manages pharmacy benefits for Blue Cross insurance plans nationwide.

"It's concerning to us from a waste standpoint," he said.

The surging popularity of the drugs raised costs for health insurers and employers over the past two years, prompting some of them to halt coverage or limit how much they would pay. Even among health care providers, Hennepin Healthcare stopped covering GLP-1 medications for weight loss alone this year for its workers, and Mayo Clinic limited lifetime GLP-1 benefits in one plan to $20,000 per worker.

Cost issues and restrictions alone don't explain the 85% quit rate after two years, or the 47% continuation rate at just six months, Gleason said. The study focused on 3,364 patients who started on GLP-1 medications for weight loss in 2021, and their Blue Cross plans didn't make wholesale changes to their drug formularies or coverage limits in the two years that followed, Gleason said.

The study excluded patients who have diabetes because the medication offers additional benefits for that population. One version, Ozempic, is federally approved only for diabetes management but is widely prescribed off-label for weight loss.

Prime didn't ask patients why they quit, but Gleason said side effects and hassles with the injections were likely factors. The quit rate was higher with the daily drugs compared with the once-a-week versions. Some also likely quit after hitting short-term weight loss goals, not appreciating the risks of gaining weight back.

Shortages also have emerged because of the immense popularity of the medications, which have been promoted on social media platforms as short-term miracles even though they are supposed to be long-term treatments. They likely contributed to the 26% of people in the Prime study who switched GLP-1 medications over two years.

Cost played a role for Maja Smedberg, who last year protested the decision by her employer, Hennepin Healthcare, to stop covering the drug that helped her lose more than 30 pounds. She has stretched out injections from seven to 10 days now that she has lost coverage, but her supply will run out in two weeks. She said she has learned a lot about portion control and said she hopes good eating and exercise habits will help once she is off the drug.

"I know the statistics regarding weight gain after going off, but you never know if I'll be an anomaly," she said. "I am worried about it, but trying not to be because worrying just stresses me out and I can't control how my body will respond."

Novo Nordisk, the Danish manufacturer of Wegovy and Ozempic, reported in 2022 that people gained two-thirds of their weight back on average after halting the medication. A global research group last year reported fewer heart problems in people with obesity who took GLP-1 injections, but they needed to be on the medications for three years to gain those benefits, Gleason said.

Researchers are trying to find alternatives or exercise regimens that will help people maintain their weight loss and manage their cravings and hunger once off the injections.

Epic Research found that 27% of patients regained all of their weight after weaning off GLP-1 medications, but that rate was cut to 19% when they switched to another weight-loss drug called phentermine. While only an 8-percentage-point difference, the risk reduction is enough for doctors to at least consider this follow-up therapy for patients, said Kersten Bartelt, lead author of the Epic report.

A Danish study found that a combination of GLP-1 injections and structured exercise allowed many patients to maintain their weight loss for at least one year after discontinuing the drugs.

Gleason said that is encouraging and that Prime is promoting a KeepWell program to employers that can help their workers make diet and exercise improvements while receiving obesity medications. He likened the pairing of GLP-1 medications with structured exercise and diet programs to the counseling programs that were first combined with nicotine therapies years ago.

"Quitting smoking is hard," he said. "Losing weight is hard."