In patients without diabetes being treated with GLP-1s for overweight/obesity, persistence rates (rates of patients remaining on the drugs without treatment gaps) have significantly improved over the last 5 years, results from two new studies showed.

“This real-world analysis of high-potency, weight loss-indicated GLP-1 products among individuals without diabetes found that 1-year treatment persistence has nearly doubled from 2021 to the first half of 2024,” reported the authors of the first of the two studies, recently published in the Journal of Managed Care & Specialty Pharmacy.

Of note, the persistence rates don’t necessarily suggest that those who did have more than 60-day gaps discontinued treatment altogether, first author Landon Z. Marshall, PharmD, PhD, of Prime Therapeutics in Eagan, Minnesota, told Medscape Medical News. 

During the gap, “individuals may have stayed on GLP-1 therapy by obtaining their GLP-1s outside of their insurance benefit, such as by directly purchasing from the manufacturer or a compounding pharmacy,” Marshall explained.

The resolution of supply shortages, as well as evolving, improved patient management, are seen as major drivers in the improvement in persistence of treatment.

Data From the Prime Therapeutic Database

For their study, Marshall and colleagues evaluated data from the Prime Therapeutic database for 33,607 insured patients without diabetes who had initiated GLP-1 treatment with semaglutide or tirzepatide between January 2021 and June 2024.

Of these patients, 75.5% were female, and their mean age was 45.7 years.

Overall, the rates of 1-year persistence, defined as having no gaps in coverage of more than 60 days in the 12 months following treatment initiation, nearly doubled from 33.2% in 2021 to 60.9% in the first half of 2024.

Specifically, for those on semaglutide, 1-year persistence rates increased from 33.2% in 2021 to 34.1% in 2022, to 39.8% in 2023, and to 58.6% by the first half of 2024.

For tirzepatide, the 1-year persistence rates, beginning in 2023, when the drug became available, were higher, at 64%, and increased to 64.8% by the first half of 2024.

“To our knowledge, this is the first study to assess persistence, adherence, and switching among individuals initiating GLP-1 weight-loss products as recently as the first half of 2024,” the authors noted.

“By including the first half of the 2024 index period, our study provides insight into persistence and adherence with the contemporary high-potency, weight loss-indicated GLP-1 product mix.”

The doubling of persistence rates observed in the study is encouraging, suggesting “a significant reduction in the number of patients discontinuing treatment among patients initiating treatment in more recent years,” the study authors wrote.

“Furthermore, adherence during the first year of therapy also improved over time, with the highest rates observed among the most recent initiators (55.5% in the first half of 2024) relative to rates in earlier years (30.2% in 2021),” they added.

“This suggests that in addition to greater persistence, more patients regularly take medication as prescribed throughout the year in more recent years as well.”

Clinicians can play a key role in further improving adherence to the drugs, said Marshall, by “developing a comprehensive patient obesity treatment plan, including diet and exercise, preparing patients for expected side effects, and managing them; structuring follow-up and ongoing support, and reinforcing lifestyle modification behaviors.”

Trends in Switching Medications Also Evolving

In the second study, published in JAMA Network Open, researchers evaluated data from another commercial claims database (Merative MarketScan Commercial Claims and Encounters Database), of 126,984 patients without diabetes, enrolled between 2019 and 2024, who were overweight or obese, and who had initiated GLP-1 therapy after being continuously enrolled in the database for at least 12 months.

The study investigators found that, overall, 20.6% of patients switched GLP-1 agents within 12 months of initiation of the drugs, while the overall rate of 12-month persistence across the entire cohort was much lower than rates observed in Marshall’s study, at just 24.6%.

The most common initial transition was from liraglutide to semaglutide, occurring in 24.4% of patients.

Notably, persistence rates were higher among those who switched drugs vs nonswitchers (36.4% vs 21.4%), and switchers also had a higher rate of treatment adherence, representing the proportion of days covered, at 63% vs 52% for nonswitchers (P < .001 for both).

Optimal adherence, defined as a proportion of days covered of 80% or more, was also higher in switchers vs nonswitchers (33.3% vs 28.6%; P < .001).

“Switching between GLP-1 agents was common and may reflect active therapy management rather than nonengagement, particularly as new formulations and weight management agents emerge,” noted the study authors, led by Sarah E. Messiah, PhD, of The University of Texas Southwestern Medical Center, Dallas.

“In this large cohort of adults with overweight or obesity without diabetes, fewer than 1 in 4 patients remained on any GLP-1 after 12 months,” they reported.

Considering the higher rate of persistence observed in switching therapies, “these findings support reframing switching as part of long-term optimization rather than discontinuation,” they added.

“Clinicians should encourage continuity across switches and address coverage, cost, and adverse effect barriers that limit persistence.”

Persistence Rates ‘Encouraging’

Commenting on the research, Arya M. Sharma, MD, professor emeritus at the University of Alberta in Edmonton, Alberta, Canada, noted “it’s very encouraging to see these numbers going up.” Initially, drug shortages and other issues made things difficult, but the current data are “very encouraging,” he added.

“Like treatment of every other chronic disease, it’s not realistic to expect persistence figures to go up to 100%, but the 50% to 60% [observed in the research] is not so bad,” he told Medscape Medical News.

The higher persistence among those switching makes sense, said Sharma. “If you switch, it does indicate that you’re willing to continue, so it’s not necessarily surprising that switching was associated with higher persistence.”

Better to switch drugs and remain on treatment than to discontinue, he noted.

“The greater concern would be discontinuation because the data is pretty consistent that when people discontinue these medications, they’re very likely to put the weight back on,” he said. “So if switching can help people to better tolerate a drug or have improved efficacy, then that’s a better outcome.”

Marshall reported being an employee of Prime Therapeutics. The JAMA Network Open study’s authors’ disclosures are detailed in the published study. Sharma reported being a consultant and speaker for both Novo Nordisk and Lilly as well as other companies in the obesity space.