PMID-35015037 – STEP 8 Semaglutide vs Liraglutide
Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA, 2022;327(2):138-150.
Quick Reference
| Property | Value |
|---|---|
| PMID | 35015037 |
| DOI | 10.1001/jama.2021.23619 |
| Year | 2022 |
| Journal | JAMA |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=338 adults with overweight/obesity without diabetes |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Semaglutide 2.4 mg weekly produced -15.8% mean body weight change vs -6.4% with liraglutide 3.0 mg daily at 68 weeks (treatment difference: -9.4 percentage points; p<0.001)
- 87.2% of semaglutide participants achieved >=5% weight loss vs 58.1% with liraglutide
- 70.9% achieved >=10% weight loss vs 25.6% with liraglutide
- 55.0% achieved >=15% weight loss vs 12.0% with liraglutide
- Both treatments had similar overall adverse event profiles, though nausea was more common with semaglutide (44% vs 38%) while injection-site reactions were more common with liraglutide
- Semaglutide offered the convenience of weekly vs daily injection
Study Design
Randomized, open-label, phase 3b trial at 19 US sites. Adults aged 18+ with BMI >=30 (or >=27 with comorbidity) without diabetes were randomized 3:1:3:1 to semaglutide 2.4 mg weekly, semaglutide placebo weekly, liraglutide 3.0 mg daily, or liraglutide placebo daily for 68 weeks with lifestyle intervention. Open-label for active treatments, blinded for placebo comparisons. Co-primary endpoints: percent change in body weight and proportion achieving >=5% weight loss at week 68.
Limitations
- Open-label design for active drug comparisons introduces potential bias (participants and investigators aware of treatment assignment)
- Relatively small sample size for a head-to-head comparison
- US-only enrollment
- Does not compare injectable semaglutide to oral semaglutide formulations
- 68-week duration; longer-term comparative data not available
Clinical Relevance
STEP 8 provides the first head-to-head comparison of the two FDA-approved GLP-1 RA obesity treatments, establishing clear superiority of semaglutide 2.4 mg weekly over liraglutide 3.0 mg daily. The ~2.5-fold greater weight loss with semaglutide, combined with the convenience of weekly dosing, positions it as the preferred GLP-1 RA for obesity pharmacotherapy.
Related
#research #RCT #semaglutide #evidence-level-I