PMID-33667417 – STEP 2 Semaglutide in T2D and Obesity
Davies M, Faerch L, Jeppesen OK, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet, 2021;397(10278):971-984.
Quick Reference
| Property | Value |
|---|---|
| PMID | 33667417 |
| DOI | 10.1016/S0140-6736(21)00213-0 |
| Year | 2021 |
| Journal | Lancet |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=1,210 adults with T2D and overweight/obesity (BMI >=27 kg/m2) |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Semaglutide 2.4 mg produced mean weight loss of -9.6% vs -3.4% (semaglutide 1.0 mg) vs -3.4% (placebo) at 68 weeks
- 68.8% of the 2.4 mg group achieved >=5% weight loss vs 57.1% (1.0 mg) vs 28.5% (placebo)
- HbA1c reduction of -1.6 percentage points with 2.4 mg vs -1.5 (1.0 mg) vs -0.4 (placebo)
- Semaglutide 2.4 mg was superior to both 1.0 mg and placebo for the co-primary endpoints of percent weight change and achieving >=5% weight loss
- GI adverse events (nausea, diarrhea, vomiting) were the most common side effects, occurring in ~63% of the 2.4 mg group
Study Design
Randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial across 149 sites in 12 countries. Adults with T2D (HbA1c 7-10%), BMI >=27 kg/m2, and on stable antidiabetic medication were randomized 1:1:1 to subcutaneous semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo once weekly for 68 weeks, plus lifestyle intervention. Co-primary endpoints: percent change in body weight and proportion achieving >=5% weight loss.
Limitations
- Enrolled only adults with T2D; weight loss magnitude is typically lower in diabetic vs non-diabetic populations
- 68-week duration does not address long-term weight maintenance beyond the trial
- High rate of GI side effects may limit tolerability in clinical practice
- Predominantly White and Hispanic participants; limited racial diversity
Clinical Relevance
STEP 2 established that semaglutide 2.4 mg is effective for clinically meaningful weight loss in adults with T2D and obesity, a population that historically achieves less weight loss with anti-obesity medications. The dual benefit of weight reduction and glycemic improvement positions it as a key treatment option for this comorbid population.
Related
#research #RCT #semaglutide #evidence-level-I