In adults with obesity (BMI ≥30 kg/m²), daily subcutaneous semaglutide significantly promoted weight loss compared to liraglutide and placebo, with gastrointestinal symptoms as the main side effect.
PICO Summary
Population:
Adults without diabetes, BMI ≥30 kg/m².
Intervention:
Once-daily semaglutide injections (doses from 0.05 to 0.4 mg), with dose escalation every 4 weeks.
Comparison:
Daily liraglutide 3.0 mg and placebo.
Outcome:
- Efficacy: Weight loss was dose-dependent, with a maximum of −13.8% weight reduction for semaglutide 0.4 mg, significantly greater than liraglutide’s −7.8% and placebo’s −2.3% (p<0.0001 for semaglutide vs placebo).
- Safety and Tolerability: Gastrointestinal symptoms, primarily nausea, were the most common adverse events, following a dose-dependent trend.
Clinical Summary
Main Finding:
Semaglutide, at doses up to 0.4 mg daily, demonstrated significantly greater weight loss than liraglutide 3.0 mg and placebo over a 52-week period, indicating it as a potent option for obesity management.
Clinical Relevance:
These results support the potential of semaglutide as an effective weight-loss agent in adults with obesity, offering greater reductions in body weight compared to liraglutide. This efficacy comes with a predictable safety profile typical of GLP-1 agonists, particularly regarding gastrointestinal symptoms, which need management consideration.
Study Overview:
- Type of Study: Phase 2, randomised, double-blind, placebo- and active-controlled.
- Sample Size & Population: 957 adults with obesity (BMI ≥30 kg/m²) across multiple centres in eight countries.
- Intervention Duration & Doses: 52 weeks with daily semaglutide at doses ranging from 0.05 mg to 0.4 mg, escalating every 4 weeks.
- Comparison: Daily liraglutide at a fixed dose of 3.0 mg and placebo with matched dosing schedules.
Outcomes:
- Primary Measure (Weight Loss):
- Semaglutide vs. Placebo: All semaglutide doses led to significant weight reduction compared to placebo, with dose-dependent outcomes:
- 0.4 mg dose achieved the highest weight loss, averaging −13.8%.
- Lower doses also achieved significant reductions, with weight loss ranging from −6.0% to −13.8% across doses (p<0.0001).
- Only 2.3% weight loss was observed in the placebo group.
- Semaglutide vs. Liraglutide: Semaglutide doses of 0.2 mg and above achieved significantly more weight loss than liraglutide (−11.2% to −13.8% vs −7.8% with liraglutide).
- Semaglutide vs. Placebo: All semaglutide doses led to significant weight reduction compared to placebo, with dose-dependent outcomes:
- Secondary Measure (Percentage of Patients Achieving Weight Loss Targets):
- ≥10% Weight Loss: Achieved by 37–65% of patients on semaglutide 0.1 mg and above, compared to 10% in the placebo group (p<0.0001).
- ≥5% Weight Loss: Higher proportions of patients achieved 5% weight loss with semaglutide across all doses compared to placebo.
- Safety Profile:
- Gastrointestinal symptoms were dose-related and most common with semaglutide, particularly nausea, which was the primary adverse effect and similar to previous findings with GLP-1 receptor agonists.
- Semaglutide’s gastrointestinal effects led to higher rates of dose adjustments and some treatment discontinuations.
Considerations:
The study’s dose-ranging phase 2 design requires further validation in larger, longer-term phase 3 studies to establish optimal dosing, long-term safety, and effectiveness, especially in different obesity subgroups.
Reference:
O’Neil, P. M., et al. (2018). The Lancet, 392(10148), 637–649. doi:10.1016/S0140-6736(18)31773-2.
Disclosure: This article on Hormone Insight was created with both human and AI assistance. The human expert editor reviewed the article before publication to ensure accuracy, quality, and clarity.
