Summary:
In 957 adults without diabetes with obesity (BMI ≥30) across 71 sites in 8 countries, once-daily subcutaneous semaglutide (0.05-0.4 mg) for 52 weeks achieved dose-dependent weight loss up to 13.8% (0.4 mg) vs 7.8% with liraglutide vs 2.3% with placebo (P<0.0001); 65% achieved ≥10% weight loss vs 34% (liraglutide) vs 10% (placebo) compared to liraglutide 3.0 mg daily and placebo, with dose-dependent GI adverse events most common at higher semaglutide doses.
| PICO | Description |
|---|---|
| Population | 957 adults without diabetes with obesity (BMI ≥30), 71 sites in 8 countries. |
| Intervention | Daily subcutaneous semaglutide (0.05-0.4 mg) with 4-week dose escalation for 52 weeks. |
| Comparison | Liraglutide 3.0 mg daily (approved obesity dose) and placebo. |
| Outcome | Weight loss 13.8% vs 7.8% vs 2.3%. ≥10% responders: 65% vs 34% vs 10%. |
Semaglutide vs Liraglutide for Weight Loss
RCT · obesity · 52 weeks
Once-daily semaglutide 0.4 mg produced nearly double the weight loss of liraglutide 3.0 mg at 52 weeks (13.8% vs 7.8%), with dose-dependent GI side effects. These phase 2 data set the stage for the weekly semaglutide obesity programme.
Clinical Context
Before semaglutide, liraglutide was the only GLP-1 RA approved for obesity. Semaglutide’s longer half-life suggested greater potential.
Clinical Pearls
1. Semaglutide Substantially Outperforms Liraglutide: Near-doubling of efficacy (13.8% vs 7.8%).
2. Dose-Response Guides Optimization: Clear dose-dependent efficacy (6.0-13.8%) informed Phase 3 development.
3. High Responder Rates: 65% achieved ≥10% weight loss threshold for comorbidity improvement.
4. GI Tolerability Correlates With Efficacy: Higher doses require gradual titration for tolerability.
Practical Application
Phase 2 data informed 2.4 mg weekly approval (Wegovy). Liraglutide non-responders can expect substantially greater efficacy with semaglutide.
Study Limitations
Phase 2 small sample sizes per arm. 52-week duration. Excluded diabetes. Daily dosing differs from approved weekly.
Bottom Line
Semaglutide produces substantially greater weight loss than liraglutide with dose-dependent effects reaching 13.8%.
Source: O’Neil PM, et al. “Semaglutide vs Liraglutide for Weight Loss in Obesity: Phase 2 Trial.” Lancet, 2018. Read article