Key result
Off-label GLP-1 receptor agonist prescribing surged ~15-fold from 2021 to 2025, driven by advantaged populations.
Cohort (n=92,415,648)
Yes
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Off-label prescribing of GLP-1 receptor agonists has increased rapidly, particularly among socioeconomically advantaged populations and individuals without obesity, raising concerns about the risk-benefit profile in these groups.
Objective This study evaluated temporal trends and patient characteristics associated with glucagon‐like peptide‐1 (GLP‐1) receptor agonist prescribing among US adults without an apparent FDA‐approved indication. Methods This retrospective cohort study used Cosmos electronic health records (01/2021–12/2025). Adults prescribed liraglutide, semaglutide, or tirzepatide without a documented indication (type 2 diabetes or obesity with qualifying comorbidities) were included. Patients without a recorded weight ≥ 6 months prior to first prescription were excluded. Demographic and clinical characteristics were compared using t ‐tests and χ 2 tests. Results Among 92,415,648 adults without an apparent FDA‐approved indication, 1,133,953 (1.2%) were prescribed GLP‐1 receptor agonists. Prescribing increased from 0.1% in 2021 to 1.5% in 2025 (15‐fold). Recipients had higher median BMI (25.9 vs. 24.5 kg/m 2 ) and were more often female (85.5%) and White (60.0%). Hypertension and dyslipidemia were more common, while coronary artery disease and heart failure were less prevalent. Notably, 35.1% had normal BMI; eating disorders were more frequent (1.8% vs. 0.3%). GLP‐1 receptor agonist use was associated with lower social vulnerability and private insurance. Conclusions GLP‐1 receptor agonist prescribing without an apparent FDA‐approved indication has increased rapidly and disproportionately involves socioeconomically advantaged populations, including individuals without obesity. The risk–benefit profile in these populations remains uncertain.
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Orandi et al. (2026) conducted a cohort in Without an apparent FDA-approved indication for GLP-1 receptor agonists (n=92,415,648). GLP-1 receptor agonists vs. 2021 baseline was evaluated on GLP-1 receptor agonist prescribing rate (15-fold increase). GLP-1 receptor agonist prescribing among US adults without an FDA-approved indication increased 15-fold from 0.1% in 2021 to 1.5% in 2025, disproportionately involving advantaged populations.
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