Two-Year Effects of Semaglutide in Adults with Overweight or Obesity (STEP 5) — VialBase Research
high
- Semaglutide 2.4mg produced sustained 15.2% weight loss over 2 years
- Weight loss maintained without plateau through 104 weeks
- 77.1% achieved >=5% weight loss at 104 weeks
Summary
STEP 5 evaluated the long-term (2-year) efficacy and safety of once-weekly semaglutide 2.4 mg for weight management in adults with overweight or obesity without diabetes. This trial addressed a critical question about durability of weight loss, demonstrating sustained efficacy over 104 weeks.
Key Findings
- Mean weight change at 104 weeks: -15.2% with semaglutide vs -2.6% with placebo
- 77.1% achieved ≥5% weight loss (vs 34.4% placebo) at 2 years
- 61.8% achieved ≥10% weight loss; 52.1% achieved ≥15% at 2 years
- Weight loss was maintained from week 68 through week 104 without significant regain
- Sustained improvements in waist circumference and cardiometabolic parameters
- Safety profile consistent with STEP 1; no new safety signals with longer duration
Methodology
Double-blind, placebo-controlled RCT. 304 adults randomized 1:1 to semaglutide 2.4 mg or placebo, both with lifestyle intervention. 104-week treatment period, the longest in the STEP program. Dose escalation over 16 weeks to target dose.
Limitations
- Smaller sample size than STEP 1 (304 vs 1,961)
- Does not address what happens after discontinuation (STEP 4 showed regain)
- Population without diabetes — results may differ in T2DM
- Lifestyle intervention in both arms
- Limited ethnic/racial diversity
Relevance to Content
Addresses the key consumer concern of “does the weight stay off?” Demonstrates durable 2-year efficacy, but must be paired with STEP 4 data showing regain upon discontinuation. Essential for long-form content about semaglutide treatment planning and expectations.
See Also
- Parent compound: Semaglutide