Among 743,153 US adults with obesity (no diabetes) who started injectable semaglutide or tirzepatide in 2024, only 29.9% and 35.9% respectively maintained prescriptions at 12 months. FDA-labeled maintenance doses were reached by just 28.3% (semaglutide) and 55.0% (tirzepatide). Critically, only 8.8% and 16.4% of initiators were simultaneously persistent, at maintenance dose, and had a recorded weight at 12 months — the minimum standard for meaningful outcome assessment. Documented ≥5% total body weight loss was seen in just 25.6% and 30.4% of all initiators, but jumped to 82.9% and 87.3% among the small subset completing every step of care.
These findings expose a stark gap between landmark trial results — where semaglutide and tirzepatide produced 15–22% weight loss under controlled conditions — and the messier reality of clinical practice. The data suggest that discontinuation, dose-escalation failure, and poor monitoring are the primary bottlenecks, not the drugs themselves. For patients and clinicians, this reframes GLP-1 therapy as a system-level challenge requiring structured follow-up protocols, not merely a prescription decision. Tirzepatide outperformed semaglutide on every measure, consistent with its superior trial efficacy. Limitations include the retrospective EHR design, which cannot capture out-of-network prescriptions or patient-reported reasons for stopping. About half of patients lacked a 12-month weight, introducing substantial selection bias in outcome estimates. As a preprint not yet peer-reviewed, these findings should be interpreted cautiously — but the scale of the cohort lends considerable weight to the central message.