Trends in 1-year persistence and adherence among initiators of high-potency, weight loss–indicated glucagon-like peptide 1 receptor agonists

BACKGROUND: Despite the clinical efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for weight loss, real-world persistence remains substantially lower than seen in clinical trials. Since 2021, GLP-1RA shortages and changes in product availability have complicated access and persistence. OBJECTIVE: To describe by calendar year of initiation the 1-year treatment persistence and adherence trends among commercially insured members without diabetes newly initiating high-potency, weight loss-indicated GLP-1RA products, semaglutide (Wegovy) and tirzepatide (Zepbound). METHODS: This cohort study used Prime Therapeutics’ integrated medical and pharmacy claims data from an average monthly membership of 17.9 million commercially insured individuals to identify members without diabetes who newly initiated high-potency, weight loss-indicated GLP-1RA treatment between January 1, 2021, and June 30, 2024 (index date period), defined in year increments, 2021, 2022, 2023, and the first half of 2024 (1H 2024). Members were included in the study sample if they were continuously enrolled with no more than 15 days total enrollment gap during the 365-day preperiod and the 365-day postperiod after their index GLP-1RA claim with no prior GLP-1RA drug claim 365 days before index. Members were excluded if they had a preperiod diabetes diagnosis medical claim or diabetes drug claim or if they were aged less than 19 years at index. The primary outcome of GLP-1RA persistence was measured as no more than a 60-day gap between the end of a GLP-1RA claim’s days supply and the subsequent claim fill date in the 365-day period following index. Adherence was defined as proportion of days covered of at least 80%. Across all measures GLP-1RA product switching was allowed. RESULTS: Among the 62,650 members without diabetes newly initiating a high-potency, weight loss-indicated GLP-1RA between 2021 and June 30, 2024, 33,607 (53.6%) met the full study criteria. The mean age was 45.7 years, and 75.5% were female. Across the index years, 1-year persistence increased from 33.2% in 2021 to 60.9% in 1H 2024. Semaglutide 1-year persistence rates from 2021 to 1H 2024 were 33.2%, 34.1%, 39.8%, and 58.6%, respectively. For tirzepatide, 1-year persist- ence rates in 2023 and 1H 2024 (the only years the product was available) were 64.0% and 64.8%, respectively. CONCLUSIONS: This real-world analysis of high-potency, weight loss-indicated GLP-1RA products among individuals without diabetes found that 1-year treatment persistence has nearly doubled from 33.2% in 2021 to 60.9% in 1H 2024. GLP-1RA product shortage resolution may have improved persistence rates. Other potential influencing factors include improved GLP-1RA dose escalation and side effect management, as well as weight loss lifestyle management programs. Additional research is needed to understand treatment discontinuation reasons and long-term GLP-1RA cost-effectiveness.