PMID-33625476 – STEP 3 Semaglutide Plus Intensive Behavioral Therapy
Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA, 2021;325(14):1403-1413.
Quick Reference
| Property | Value |
|---|---|
| PMID | 33625476 |
| DOI | 10.1001/jama.2021.1831 |
| Year | 2021 |
| Journal | JAMA |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=611 adults with overweight/obesity without diabetes |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Semaglutide 2.4 mg + intensive behavioral therapy (IBT) with initial low-calorie diet produced -16.0% mean weight change vs -5.7% with placebo + IBT at 68 weeks
- 86.6% of semaglutide participants achieved >=5% weight loss vs 47.6% with placebo
- 75.3% achieved >=10% weight loss vs 27.0% with placebo
- 48.2% achieved >=15% weight loss vs 14.1% with placebo
- Cardiometabolic risk factors (waist circumference, blood pressure, lipids, CRP, HbA1c) improved significantly more with semaglutide + IBT
Study Design
Randomized, double-blind, placebo-controlled, 68-week trial at 41 US sites. Adults (BMI >=30, or >=27 with comorbidity) without diabetes were randomized 2:1 to semaglutide 2.4 mg or placebo, both combined with intensive behavioral therapy (30 counseling visits) and an initial 8-week low-calorie diet (1,000-1,200 kcal/day). Co-primary endpoints: percent change in body weight and proportion achieving >=5% weight loss at week 68.
Limitations
- US-only enrollment limits geographic generalizability
- Intensive behavioral therapy (30 visits) is resource-intensive and may not be feasible in routine clinical settings
- Initial low-calorie diet phase complicates attribution of early weight loss to drug vs diet
- Without diabetes population only; unclear if similar additive effects occur in T2D
Clinical Relevance
STEP 3 demonstrates that combining semaglutide with intensive behavioral therapy and an initial low-calorie diet produces the largest weight reductions in the STEP program, supporting a multimodal treatment approach. Nearly half of participants lost >=15% of body weight, approaching results previously achievable only with bariatric surgery.
Related
#research #RCT #semaglutide #evidence-level-I