Weight Management with Reduced-Dose Oral Semaglutide
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on October 10th, 2025
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Semaglutide, initially approved as a subcutaneous injection for type 2 diabetes, is now also available in an oral formulation. Beyond glycemic control, semaglutide has been shown to promote significant weight reduction. A recent Novo Nordisk–funded study evaluated the effect of a lower oral dose of semaglutide in managing obesity.
The trial enrolled 307 participants with a body mass index (BMI) greater than 30, or greater than 27 in the presence of obesity-related comorbidities such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. The cohort had a mean body weight of 106 kg and an average BMI of 37.5. Approximately 2% of participants had diabetes, 47% had prediabetes, and the remainder had normal glucose levels.
Participants were randomized to receive either placebo or 25 mg of oral semaglutide once daily. All participants also received lifestyle counseling, including guidance on diet (500-kcal daily deficit) and physical activity (150 minutes per week). The medication was taken with 120 mL of water in the morning, following an overnight fast and at least 30 minutes before food, beverages, or other oral medications.
After 64 weeks, oral semaglutide resulted in a mean weight reduction of 13.6%, compared with 2.2% in the placebo group. Adverse events were more common in the semaglutide group, particularly gastrointestinal effects such as nausea, vomiting, constipation, dyspepsia, and diarrhea. The authors suggested that future research should compare oral semaglutide against active comparators, including other GLP-1 receptor agonists and the injectable form of semaglutide.
The trial enrolled 307 participants with a body mass index (BMI) greater than 30, or greater than 27 in the presence of obesity-related comorbidities such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. The cohort had a mean body weight of 106 kg and an average BMI of 37.5. Approximately 2% of participants had diabetes, 47% had prediabetes, and the remainder had normal glucose levels.
Participants were randomized to receive either placebo or 25 mg of oral semaglutide once daily. All participants also received lifestyle counseling, including guidance on diet (500-kcal daily deficit) and physical activity (150 minutes per week). The medication was taken with 120 mL of water in the morning, following an overnight fast and at least 30 minutes before food, beverages, or other oral medications.
After 64 weeks, oral semaglutide resulted in a mean weight reduction of 13.6%, compared with 2.2% in the placebo group. Adverse events were more common in the semaglutide group, particularly gastrointestinal effects such as nausea, vomiting, constipation, dyspepsia, and diarrhea. The authors suggested that future research should compare oral semaglutide against active comparators, including other GLP-1 receptor agonists and the injectable form of semaglutide.