Real‐World Semaglutide Initiation Behaviours in the United States: Impact on Early Treatment Discontinuation and on 1‐Year Persistence

ABSTRACT Aims Little is known about how glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are initiated in real‐world settings and whether prescribing behaviours in routine care contribute to the high discontinuation rates seen in practice. We examined prescribing behaviours for injectable semaglutide at treatment initiation and evaluated their impact on early medication discontinuation and on 1‐year persistence among US adults. Materials and Methods Using MarketScan data (2018–2021), this retrospective cohort study identified US adults with diabetes and/or obesity on no prior incretin therapy starting injectable semaglutide. Initiating dose was categorized as low or high (≤ 0.5 and ≥ 1.0 mg/week, respectively); treatment status was followed for 12 months. Medication persistence was estimated using Kaplan–Meier analysis. Piecewise Cox proportional hazards regression assessed early discontinuation risk, logistic regression assessed the odds of high‐dose initiation. Results Among this cohort of 48 658 adults, 14.5% were started on semaglutide using high doses. The off‐label high‐dose regimen was associated with decreased 1‐year persistence ( p = 0.01), and a 25% increase in early discontinuation risk (HR: 1.25, 95% CI: 1.17–1.34, p < 0.001) independently of age, obesity status, co‐morbidity measures and cost. Odds of high‐dose initiation were increased in the West and South ( p < 0.001), for endocrinologists ( p = 0.02), for patients who were male ( p < 0.001), younger ( p = 0.02), with obesity versus overweight ( p = 0.002), and for treatment initiation in 2018 compared with 2019–2021 ( p < 0.001). Conclusion Initiation of injectable semaglutide therapy using high doses is common in real‐world settings. High‐dose initiation represents a modifiable risk factor for early medication discontinuation and decreased 1‐year persistence.