Oral Semaglutide Achieves Superior Weight Loss Compared With Placebo in Phase 3 Trial

Oral semaglutide 50mg achieved superior weight loss in adults with obesity or overweight with 1 or more comorbidities compared with placebo, according to results from the phase 3a OASIS 1 trial.

The 68-week OASIS 1 trial (ClinicalTrials.gov Identifier: NCT05035095) included 667 patients 18 years of age and older with a body mass index (BMI) of greater than or equal to 30kg/m², or a BMI of greater than or equal to 27kg/m² with the presence of at least 1 weight-related complication (eg, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease). Patients were randomly assigned to receive either semaglutide 50mg orally once daily or placebo, in addition to lifestyle intervention.

According to the trial product estimand (the effect if all participants adhered to treatment as intended) from a mean baseline body weight of 105.4kg, patients treated with semaglutide 50mg achieved a statistically significant weight loss of 17.4% after 68 weeks compared with a 1.8% reduction with placebo. Moreover, 89.2% of patients treated with semaglutide 50mg achieved a weight loss of 5% or more after 68 weeks compared with 24.5% of those treated with placebo.

Using the treatment policy estimand (treatment effect regardless of treatment adherence), patients treated with semaglutide 50mg achieved a statistically significant weight loss of 15.1% after 68 weeks compared with a 2.4% reduction with placebo. Moreover, 84.9% of patients treated with semaglutide 50mg achieved a weight loss of 5% or more after 68 weeks compared with 25.8% of those treated with placebo.

As for safety, oral semaglutide was reported to be safe and well tolerated. Mild to moderate gastrointestinal adverse reactions were most commonly observed during the study.

“We are very pleased with the weight loss demonstrated by the once-daily oral formulation of semaglutide in obesity. The results show comparable weight loss as in the STEP 1 trial with injectable semaglutide 2.4 mg in obesity branded as Wegovy^®”, said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences.”

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is currently marketed under the trade name Wegovy (for subcutaneous injection) as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in: 

• Adults with an initial body mass index (BMI) of 30kg/m² or greater (obese) or 27kg/m² or greater (overweight) in the presence of at least 1 weight-related comorbid condition (eg, hypertension, T2DM, dyslipidemia); and 
• Pediatric patients with an initial BMI at the 95th percentile or greater standardized for age and sex (obesity).