Prime Study Finds Low Long-Term Adherence to GLP-1 Obesity Drugs

A new analysis highlights a major challenge in the real-world effectiveness of the GLP-1 drugs used to treat obesity: most patients without diabetes stop treatment within the first few years, according to a review of claims data by Prime Therapeutics.

GLP-1 agonists, such as Wegovy (semaglutide) and Zepbound (tirzepatide), have become central to the medical treatment of obesity in the United States, with 1 in 8 adults having used one by 2024. Clinical trials show these drugs can produce 10% to 20% weight loss and reduce the risk of major cardiovascular events.

Wegovy was approved to treat obesity in June 2021, and it is available as a once-weekly, single-dose pen. Zepbound was approved in November 2023 to treat obesity.

Prime’s study analyzed pharmacy and medical claims data from its pool of 16.5 million commercially insured members to understand adherence and persistence to GLP-1 obesity medications over time. Researchers focused on 5,780 adults with obesity but no diabetes who initiated GLP-1 therapy between January 2021 and March 2022 and remained continuously enrolled for the next three years.

The results revealed that only 8.1% of these members persisted with treatment for the full three years. Weekly semaglutide products had the highest three-year persistence (14.3%), while daily liraglutide (Victoza) had the lowest at 2.5%. The average proportion of days covered (PDC) — a standard adherence measure — was 37.5%, with only 12.5% of users classified as adherent over the three years. Additionally, more than one-third of users switched GLP-1 products during the period.

Related: Prime Study Finds Lower Adherence, Higher Costs for Weight Loss Drugs | AMCP 2024

Patrick Gleason, Pharm.D.

The results weren’t a surprise, and they continued a trend seen in previous analyses, Patrick Gleason, Pharm.D., assistant vice president of health outcomes, Prime Therapeutics, said in an interview.

Earlier Prime research had already shown poor short-term persistence: in a one-year real-world study from 2023, just 32% of members remained on therapy. A follow-up study found only 15% persisted for two years. These results align with broader literature confirming the drop-off in GLP-1 use over time.

“During this time, there was a lot going on in the marketplace, with challenges to obtaining products and shortages,” Gleason said. “Doctors were still learning how to prescribe these products and manage patients. Care management and behavior management programs were not really adopted.”

In a separate analysis, Prime looked at one-year persistence across different years of initiation—from 2021 through the first quarter of 2024, focusing on those who started treatment with either Wegovy or Zepound. This analysis aimed to isolate the effect of supply availability on adherence.

This analysis found an improvement in adherence, doubling from 33.2% in 2021 to 62.7% in 2024. Gleason suggested that supply chain issues, including product shortages, were largely resolved in 2024 and likely explain improved adherence. Additionally, physicians may be getting better at managing the side effects associated with Wegovy and Zepbound, but Prime’s analysis did not assess whether anti-emetics, which help prevent nausea and vomiting, were being prescribed at a higher rate.

“This data was from claims data, so I can’t quantify this, but I suspect that prescribers of these products have become better at managing their patients and understanding the side effects,” Gleason said.

There is a better understanding that to succeed in weight loss is more than just prescribing a drug. “It's also behavior modification,” he said. “People need to make changes in their diet. They need to make changes in their exercise routine to be successful. Wrap-around services of care and management need to be applied. Many self-insured employers are making decisions to provide that coverage for behavior modification.”

There is also an evolving understanding of obesity treatment as a long-term medical intervention rather than a short-term solution. “It’s becoming clear that people need to be in therapy for more than just a few months,” Gleason said. “This is a chronic disease… If you want to get these benefits of cardiovascular debt reduction, you need to be on therapy for years, not months.”

Related: Prime Therapeutics Finds No Medical Cost Offsets for GLP-1 Obesity Drugs | AMCP Annual 2025

Gleason said the next analysis, expected in the fourth quarter of 2025, will assess cost-effectiveness and clinical event rate compared with the matched control group.

Earlier this year, Prime presented data at the Academy of Managed Care Pharmacy that found no medical cost offsets for patients taking GLP-1 drugs to treat obesity. In fact, their analysis of real-world data found an increase in total costs for patients who were taking GLP-1 therapies to treat obesity but did not have diabetes. The medical cost increased for the GLP-1 treatment group by an average of $1,338 per member, compared with a matched control group.