Although glucagon-like peptide-1 (GLP-1) agonists have shown promising results in reducing weight and cardiovascular risks, new data reveals that many U.S. adults struggle to stay on long-term treatment.
While newer obesity-indicated GLP-1 therapies, such as semaglutide and tirzepatide, are increasingly used, poor persistence rates threaten the clinical and economic benefits of these medications.
Novo Nordisk A/S’ NVO semaglutide is the main input in Ozempic and Wegovy, and tirzepatide is a key ingredient in Eli Lilly & Co’s LLY Mounjaro and Zepbound.
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GLP-1 agonists have been linked to 10% to 20% weight loss in clinical trials, with some studies also showing reduced cardiovascular events in individuals without diabetes.
Yet, despite these benefits, long-term adherence remains a major hurdle. A 2023 real-world study by Prime Therapeutics found that just 27% of users remained adherent for one year, and only 15% persisted for two years. At three years, only 8.1% of users were still on treatment.
Even the best-performing drug, Wegovy, had a three-year persistence rate of just 14.3%.
The three-year analysis included 5,780 individuals continuously enrolled in a health plan after initiating GLP-1 treatment for obesity.
The group had a mean age of 46.7 years, and nearly 80% were women. Persistence rates varied widely by medication, from 14.3% with weekly semaglutide (Wegovy) to 2.5% with daily liraglutide (Victoza).
Over three years, only 12.5% of users met the standard for adherence based on medication possession, and more than one-third switched to a different GLP-1 therapy.
However, more recent data suggests that persistence may be improving. In a separate year-over-year analysis involving 23,025 individuals initiating high-potency GLP-1s—Wegovy and Zepbound—one-year persistence rose from 33.2% in 2021 to 62.7% in 2024.
Tirzepatide (Zepbound), introduced in late 2023, had one-year persistence rates of over 62% in both 2023 and 2024.
This trend toward better short-term adherence is attributed to reduced supply shortages, improved dose escalation strategies, better side-effect management, and support programs.
Nonetheless, experts caution that poor long-term persistence among early adopters signals potential investment risk and limits the therapies’ full clinical impact.
Further research is needed to understand why so many users discontinue treatment and whether newer approaches can sustain adherence over the long term.
Price Action: LLY stock is up 1.92% at $792.37, and NVO stock is down 5.03% at $67.17 at the last check on Wednesday.
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