Oral Semaglutide Uptake Near Injectable Levels Within 3 Months

Weekly initiation of oral semaglutide among US adults eligible for obesity medications rose from nearly 0 to a peak of 4.56 per 10,000 eligible adults about 10 weeks after its approval for weight management, briefly overtaking injectable semaglutide, according to a research letter published in JAMA Network Open.¹

The FDA approved the once daily oral semaglutide 25 mg pill (Wegovy; Novo Nordisk) on December 22, 2025, as the first oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) for weight management.² The approval was based on the OASIS trial program and the SELECT (NCT03574597) trial, the company said. In the 64-week OASIS 4 (NCT05564117) trial of 307 adults with obesity or overweight and at least 1 comorbidity, participants who adhered to treatment lost a mean 16.6% of body weight, and 1 in 3 lost 20% or more. Novo Nordisk described weight loss as similar to injectable semaglutide 2.4 mg.

Oral semaglutide had been approved for type 2 diabetes (T2D) since 2019, but population-level evidence on its early adoption for obesity has been limited, the University of Pennsylvania researchers wrote.¹

Oral Semaglutide Peaked at 4.56 Initiations per 10,000 Adults in Week 10

The retrospective cohort study used deidentified electronic health record (EHR) data from Epic Cosmos, which spans more than 300 million patient records from over 2000 hospitals and 47,100 clinics. Eligible adults had a body mass index (BMI) of 30 or higher, or 27 or higher, with at least 1 obesity-related comorbidity such as hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, or heart failure. Patients with T2D or without a recorded BMI were excluded.

New initiators of oral semaglutide, injectable semaglutide, and injectable tirzepatide were identified between December 22, 2025, and March 15, 2026, with new initiation defined as a first prescription with no prescription for the same drug in the prior 12 months. The primary outcome was weekly initiation per 10,000 eligible adults.

Of 47,894,786 eligible adults (mean [SD] age, 52.4 [17.7] years; 57.7% female), 148,792 initiated oral semaglutide compared with 227,040 who initiated injectable semaglutide and 355,513 who initiated tirzepatide. Most oral semaglutide initiators received oral Wegovy (87.6%), while 12.4% received Rybelsus.

Oral semaglutide initiation peaked at 4.56 per 10,000 eligible adults (95% CI, 4.50-4.62) in week 10, March 2 to 8. Its uptake quickly approached and briefly exceeded that of injectable semaglutide, but tirzepatide had the highest weekly initiation rate throughout the study period. Among adults with no prior GLP-1 RA use, trends were similar, although oral semaglutide initiation stayed below injectable semaglutide.

53% of Oral Semaglutide Initiators Were New to GLP-1 RA Therapy

Overall, 53.0% of oral semaglutide initiators had no GLP-1 RA use in the prior 12 months. The most common prior exposures were injectable semaglutide (28.9% of all oral semaglutide initiators) and injectable tirzepatide (27.5%). The authors said this suggests early uptake reflected "both expansion to new users and switching from existing GLP-1 RA therapies."

Compared with injectable semaglutide and tirzepatide initiators, oral semaglutide initiators were older (mean age, 53.3 vs 49.7 and 50.5 years), more often female (72.7% vs 70.0% and 67.1%), had a lower mean BMI (36.6 vs 37.6 and 38.0), and were more often covered by Medicare (13.4% vs 9.3% and 10.2%). Family medicine clinicians wrote about half of the initiating prescriptions for each drug.

The researchers noted that tirzepatide's continued lead may reflect its greater weight-loss efficacy and established clinical use and that oral options, including orforglipron, approved in April 2026, may lower barriers tied to injectable therapies.

The study had several limitations. Prescribing indications were unavailable in the EHR, and prescription orders may not reflect dispensing or use. Prescriptions written outside participating Epic health systems, such as online and direct-to-consumer platforms, may have been missed, and delays in data availability may have limited capture of early uptake. The analysis was descriptive and did not adjust for confounding. The authors called for longer-term studies of persistence, adherence, and clinical outcomes with oral GLP-1 RAs in routine practice.

References

1. 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
2. Novo Nordisk A/S: Wegovy pill approved in the US as first oral GLP-1 for weight management. News release. Novo Nordisk. December 22, 2025. Accessed October 22, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916472