Oral Semaglutide Initiation Climbed Quickly After Obesity Approval but Trailed Tirzepatide

Weekly initiation of oral semaglutide (Novo Nordisk) rose rapidly among US adults eligible for obesity management medications after the FDA approved oral Wegovy for weight management on December 22, 2025, according to a retrospective cohort study in JAMA Network Open.

The authors noted that oral semaglutide was approved for type 2 diabetes in 2019. Using de-identified electronic health record data from Epic Cosmos, they identified 47,894,786 eligible adults with a body mass index (BMI) of 30 or greater, or 27 or greater with at least 1 obesity-related comorbidity, excluding those with type 2 diabetes or no recorded BMI.

Through March 15, 2026, 148,792 eligible adults initiated oral semaglutide; 87.6% received oral Wegovy and 12.4% Rybelsus. Weekly initiation peaked at 4.56 per 10,000 eligible adults (95% CI, 4.50-4.62) in the week of March 2. Oral semaglutide uptake quickly approached, and briefly exceeded, that of injectable semaglutide, while injectable tirzepatide had the highest weekly initiation rate throughout. Among adults without prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) use, oral semaglutide initiation remained below injectable semaglutide initiation.

Overall, 53.0% of oral semaglutide initiators had no GLP-1 RA use in the prior 12 months; 28.9% had used injectable semaglutide and 27.5% tirzepatide. The authors said this suggests early uptake reflected both new users and switching from existing therapies. Compared with injectable semaglutide or tirzepatide initiators, oral semaglutide initiators were older (mean age, 53.3 years), more often female (72.7%), had a lower mean BMI (36.6), and more often had Medicare coverage (13.4%).

The analysis was descriptive, without hypothesis testing or adjustment for confounding, and was not designed to assess causal effects. The authors noted that prescribing indications were unavailable and that prescription orders may not reflect dispensing or use. Prescriptions written outside participating Epic health systems, such as through online and direct-to-consumer platforms, may have been missed, and data lags may have limited capture of early uptake, they added. They called for longer-term studies of persistence, adherence, and clinical outcomes.

Source: Lei Y, Tang H, Jian X, Asch DA, Chen Y. Early adoption and diffusion of oral semaglutide in US adults with obesity. JAMA Netw Open. 2026;9(10):e2637779. doi:10.1001/jamanetworkopen.2026.37779