Novo Nordisk’s Phase III OASIS 4 Analyses Highlight Cardiometabolic Benefits of Oral Semaglutide 25 mg

Novo Nordisk has presented four new analyses from the Phase III OASIS 4 clinical trial (NCT05564117) evaluating oral semaglutide 25 mg at ObesityWeek 2025 in Atlanta, GA.¹

Cardiometabolic post hoc analysis headlines new, positive data

The breaking data were highlighted by a cardiometabolic post hoc analysis examining adult patients’ blood sugar and cardiovascular risk factors. In those with overweight or obesity, once-daily oral semaglutide 25 mg led to greater improvements in HbA1c, fasting plasma glucose, fasting serum insulin, and cardiovascular risk factors compared with placebo.

• At week 64, 71.1% of participants with prediabetes at baseline achieved normal blood glucose in the semaglutide group versus 33.3% with placebo.
• Participants receiving semaglutide 25 mg were more likely to achieve ≥15% body weight reduction than those on placebo.
• Within the semaglutide group, individuals achieving ≥15% weight loss experienced larger reductions in systolic (-10.1 mmHg vs -4.1 mmHg) and diastolic (-4.3 mmHg vs -1.1 mmHg) blood pressure.
• Greater improvements in C-reactive protein, non–HDL cholesterol, and triglycerides were also observed, particularly among participants achieving ≥15% body weight reduction.

In a press release, Domenica Rubino, MD, trial investigator and director, Washington Center for Weight Management and Research in Washington, DC, said: "As recently published in The New England Journal of Medicine, the primary results from the OASIS 4 clinical trial demonstrated weight loss efficacy of investigational oral semaglutide 25 mg as a potential therapeutic option for people with obesity and overweight. It's exciting to see these new results from the cardiometabolic post hoc analysis, which showed that while benefits were most pronounced in people who achieved greater than 15% weight loss, clear improvements in glycemic parameters and CV risk factors were observed in patients taking oral semaglutide 25 mg, regardless of how much weight was lost, based on the groups observed."

Findings from other latest analyses of OASIS 4

Additional findings from this latest readout of OASIS 4 include:

• An indirect comparison of the OASIS 4 (oral) and STEP 1 (injectable) Phase III trials showed that oral and injectable semaglutide achieved comparable outcomes in weight reduction, cardiometabolic improvements, and quality-of-life scores.
  • Across both formulations, similar proportions of participants achieved ≥5%, ≥10%, ≥15%, and ≥20% body weight reductions.
• A pooled post hoc analysis of OASIS 4 and STEP trials found significant weight loss across all menopause stages: pre-menopausal (18.2%), peri-menopausal (15.0%), and post-menopausal (15.7%).
  • More than half of women in each group achieved >15% body weight loss, with rates of 58.1%, 56.5%, and 53.4%, respectively.
• In participants with poor baseline physical function, 77.3% on oral semaglutide 25 mg reported meaningful functional improvement at 64 weeks versus 42.9% on placebo.

Initial readout of OASIS 4 showed positive results in weight loss

Earlier in September, The New England Journal of Medicine published topline findings from OASIS 4. Results showed:²

• At 64 weeks, participants taking oral semaglutide 25 mg achieved an average weight loss of 16.6% compared to 2.7% with placebo.
• Over one-third (34.4%) of participants on semaglutide experienced ≥20% weight loss versus 2.9% on placebo.
• The findings were comparable to those observed in previous trials of injectable Wegovy.

In a press release from the time of publication, Sean Wharton, lead study author and medical director of the Wharton Medical Clinic, said: “Oral semaglutide 25 mg builds on the proven efficacy and established safety and tolerability profile of semaglutide and represents a significant advancement in obesity treatment. People with overweight or obesity have individual preferences, and with oral semaglutide as a potential new treatment option, more of those who are not on treatment today may consider starting GLP-1 treatment.”

Novo submitted a New Drug Application (NDA) for the once-daily pill formulation of Wegovy in February and is expecting a decision from the FDA by the end of this year.

References

1. Novo Nordisk presents four new analyses on oral semaglutide 25 mg (Wegovy® in a pill*) at ObesityWeek® 2025, including demonstrated reductions in cardiovascular risk factors. News release. Novo Nordisk. November 5, 2025. Accessed November 6, 2025. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=916448

2. Novo Nordisk’s oral semaglutide 25 mg (Wegovy® in a pill*) delivered 16.6% weight loss in people with obesity in a newly published study. News release. Novo Nordisk. September 17, 2025. Accessed November 6, 2025. https://www.globenewswire.com/news-release/2025/09/17/3152045/0/en/Novo-Nordisk-s-oral-semaglutide-25-mg-Wegovy-in-a-pill-delivered-16-6-weight-loss-in-people-with-obesity-in-a-newly-published-study.html