Oral Semaglutide Shows Improvements in Blood Sugar, Cardiovascular Risk Factors

In an analysis of the phase 3 OASIS 4 (NCT05564117) trial, once daily oral semaglutide 25 mg treatment showed greater improvements in hemoglobin A_1c (HbA_1c), fasting plasma glucose, and fasting serum insulin for patients with overweight or obesity compared with the placebo. Further, investigators also found improvements in cardiovascular (CV) risk factors, such as C-reactive protein and serum triglycerides.¹

“Novo Nordisk has pioneered innovation in the obesity class for 25 years, and the oral semaglutide data at ObesityWeek reflect our drive to improve the lives of people living with obesity,” Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, said in a news release.¹ “The OASIS 4 results that we are sharing at this important meeting build on existing clinical trial evidence for oral semaglutide and extend findings beyond weight loss to suggested improvements in overall health.”

In the study, investigators examined how semaglutide tablets could help patients with overweight and obesity. It lasted for 72 weeks, including a 1-week screening period and 7-week follow-up period, and patients received either semaglutide as an oral tablet or the placebo. The primary end point included relative change in body weight and the number of individuals who achieved body weight loss of 5% or more. Secondary end points included patients who achieved a body weight of 10%, 15%, or 20% and above; change in impact of quality of life; change in body mass index; change in waist circumference; change in systolic and diastolic blood pressure; and more.²

“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,” Domenica Rubino, MD, director of the Washington Center for Weight Management and Research in Washington, DC, said in the news release.¹ “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.”

A total of 205 patients received oral semaglutide, and 102 patients received the placebo. The estimated mean change in body weight was approximately -13.6% and -2.2%, respectively, according to the study authors. Further, the investigators reported that patients receiving semaglutide were more likely to have body weight reductions of 5%, 10%, 15%, and 20% or more compared with the placebo. As for safety, gastrointestinal adverse effects were more common at 74% and 42.2%, respectively.³

In addition to oral semaglutide, data from the STEP UP (NCT05646706) phase 3b trial showed that the investigational higher 7.2 mg dose of the drug achieved the target BMI of less than 27 and waist-to-height ratio of less than 0.53. Patients also achieved treatment targets for healthy levels of 2 or more cardiovascular risk factors, including blood pressure, cholesterol, and blood sugar levels.⁴

READ MORE: Obesity Management Resource Center

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REFERENCES

1. Novo Nordisk presents 4 new analyses on oral semaglutide 25 mg (Wegovy in a pill) at ObesityWeek 2025, including demonstrated reductions in cardiovascular risk factors. News release. November 5, 2025. Accessed November 7, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916447

2. Research study looking at how well semaglutide tablets taken once daily work in people who have a body weight above the healthy range (OASIS 4). ClinicalTrials.gov identification: NCT05564117. Updated October 9, 2025. Accessed November 7, 2025. https://clinicaltrials.gov/study/NCT05564117

3. Wharton S, Lingvay I, Bogdanski P, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. N Engl J Med. 2025;393(11):1077-1087. doi:10.1056/NEJMoa2500969

4. Novo Nordisk Wegovy users achieved waist and BMI targets linked to improved health and low risk of obesity-related complications. News release. November 5, 2025. Accessed November 7, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916449