PMID-37385278 – OASIS 1 Oral Semaglutide 50mg for Obesity
Knop FK, Aroda VR, do Vale RD, et al. Oral semaglutide 50 mg taken once daily in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2023;402(10403):705-719.
Quick Reference
| Property | Value |
|---|---|
| PMID | 37385278 |
| DOI | 10.1016/S0140-6736(23)01185-6 |
| Year | 2023 |
| Journal | Lancet |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=667 adults with overweight/obesity without diabetes |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Oral semaglutide 50 mg daily produced mean weight loss of -15.1% vs -2.4% with placebo at 68 weeks (treatment policy estimand)
- 85% of oral semaglutide participants achieved >=5% weight loss vs 26% with placebo
- 69% achieved >=10% weight loss vs 12% with placebo
- 54% achieved >=15% weight loss vs 6% with placebo
- Weight loss with oral 50 mg was comparable to subcutaneous semaglutide 2.4 mg results from STEP 1
- GI adverse events (nausea, vomiting, diarrhea, constipation) were the most common side effects; treatment discontinuation due to AEs was 12% vs 4% for placebo
Study Design
Randomized, double-blind, placebo-controlled, phase 3 trial across 36 sites in 9 countries. Adults aged 18+ with BMI >=30 (or >=27 with comorbidity) without diabetes were randomized 1:1 to oral semaglutide 50 mg or placebo once daily for 68 weeks. Dose escalation over 24 weeks: 3 mg (weeks 0-4), 7 mg (weeks 4-8), 14 mg (weeks 8-12), 25 mg (weeks 12-16), 50 mg (weeks 16-68). Co-primary endpoints: percent change in body weight and proportion achieving >=5% weight loss at week 68.
Limitations
- 50 mg dose is substantially higher than the currently approved 14 mg oral dose for T2D; regulatory approval for this dose pending
- Strict fasting requirement (30 minutes before food/drink/other medications) may affect real-world adherence
- 68-week duration; longer-term data needed
- Moderate sample size for a pivotal obesity trial
Clinical Relevance
OASIS 1 is a pivotal trial demonstrating that an oral formulation of semaglutide can achieve weight loss comparable to the injectable form. This removes the injection barrier for patients and could significantly expand the treatable population for GLP-1 RA-based obesity management, though at a higher oral dose than currently marketed.
Related
#research #RCT #semaglutide #evidence-level-I