Published in The New England Journal of Medicine (September 17, 2025)
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has already transformed obesity management through its injectable formulation (Wegovy® 2.4 mg) and higher-dose oral option (50 mg). Now, new research highlights the effectiveness of a 25 mg daily oral dose as an alternative for individuals with overweight or obesity who may prefer pills over injections.
This pivotal OASIS 4 trial, published in NEJM, provides strong evidence supporting the efficacy and safety of this intermediate-dose oral semaglutide.
Study Overview
- Design: 71-week, double-blind, randomized, placebo-controlled trial
- Participants: Adults without diabetes, BMI ≥30, or BMI ≥27 with at least one obesity-related complication
- Sites: 22 clinical centers across four countries
- Intervention:
- Oral semaglutide 25 mg once daily + lifestyle interventions
- Placebo + lifestyle interventions
- Sample Size: 205 in the semaglutide group; 102 in the placebo group
- Primary Endpoints (at week 64):
- Percent change in body weight
- Proportion of participants achieving ≥5% weight reduction
Key Findings
- Weight Reduction:
- Semaglutide group: −13.6% mean body weight change
- Placebo group: −2.2% mean body weight change
- Estimated difference: −11.4 percentage points (P<0.001)
- Clinically Meaningful Weight Loss:
Participants receiving semaglutide were significantly more likely to achieve:- ≥5% weight loss
- ≥10% weight loss
- ≥15% weight loss
- ≥20% weight loss (all P<0.001)
- Quality of Life:
Significant improvements in physical function scores on the IWQOL-Lite-CT questionnaire. - Adverse Events:
- Gastrointestinal side effects were the most common: 74% with semaglutide vs. 42.2% with placebo
- No new safety concerns identified compared to previous GLP-1 studies.
Oral vs. Injectable Semaglutide: How Does 25 mg Compare?
| Formulation | Route | Typical Dose | Average Weight Loss (%) | Trial Evidence | Notes |
|---|---|---|---|---|---|
| Oral Semaglutide 25 mg | Tablet (daily) | 25 mg | ~13.6% (OASIS 4) | NEJM 2025 (NCT05564117) | Intermediate oral dose; convenient alternative to injections |
| Oral Semaglutide 50 mg | Tablet (daily) | 50 mg | ~15%–17% (OASIS 1) | NEJM 2023 | Highest oral dose; closer to injectable efficacy |
| Injectable Semaglutide 2.4 mg (Wegovy®) | Subcutaneous injection (weekly) | 2.4 mg | ~15% (STEP trials) | NEJM 2021 | Gold standard; robust weight-loss data |
Clinical Implications
This study confirms that oral semaglutide 25 mg is highly effective for weight management in adults with overweight or obesity—without diabetes. It offers an important non-injectable alternative for patients who:
- Prefer tablets over injections
- Need an option between lower-dose (14 mg) and high-dose (50 mg) oral semaglutide
- Have obesity-related complications requiring medical weight management
With an average 13.6% weight loss, the 25 mg dose is approaching the efficacy seen with injectable semaglutide 2.4 mg, making it a promising addition to the obesity treatment toolkit.
Takeaway
The OASIS 4 trial establishes oral semaglutide 25 mg as a powerful and convenient weight-loss therapy, bridging the gap between standard oral doses and higher-dose formulations. While gastrointestinal side effects remain common, the benefits in terms of weight reduction and improved quality of life make it a valuable therapeutic option for individuals struggling with obesity.
📌 ClinicalTrials.gov Identifier: NCT05564117
📌 Funded by Novo Nordisk