Trends in GLP-1 Receptor Agonist Prescribing Without an Apparent FDA-Approved Indication.

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 χ2 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/m2) 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.