PMID-36216945 – STEP 5 Two-Year Semaglutide Effects
Garvey WT, Batterham RL, Bhatt DL, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 2022;28(10):2083-2091.
Quick Reference
| Property | Value |
|---|---|
| PMID | 36216945 |
| DOI | 10.1038/s41591-022-02026-4 |
| Year | 2022 |
| Journal | Nature Medicine |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=304 adults with overweight/obesity without diabetes |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Semaglutide 2.4 mg weekly produced sustained mean weight loss of -15.2% vs -2.6% with placebo at 104 weeks (2 years)
- 77.1% of semaglutide participants achieved >=5% weight loss vs 34.4% with placebo at week 104
- 61.8% achieved >=10% weight loss vs 13.3% with placebo
- 36.1% achieved >=20% weight loss vs 2.3% with placebo
- Weight loss was maintained from approximately week 60 through week 104, demonstrating a plateau rather than regain
- Improvements in cardiometabolic parameters (waist circumference, HbA1c, lipids, CRP) were sustained over 2 years
Study Design
Randomized, double-blind, placebo-controlled, phase 3b trial. Adults aged 18+ with BMI >=30 (or >=27 with comorbidity) without diabetes were randomized 1:1 to subcutaneous semaglutide 2.4 mg or placebo weekly for 104 weeks, with lifestyle intervention. Primary endpoint: percent change in body weight at week 104. This was the longest-duration STEP trial, designed specifically to assess weight loss maintenance.
Limitations
- Relatively small sample size (n=304) compared to other STEP trials
- Does not address what happens after treatment discontinuation (addressed separately in STEP 4)
- Population without diabetes; sustainability in T2D patients may differ
- Predominantly White participants (~75%); limited diversity
Clinical Relevance
STEP 5 provides the critical 2-year durability data showing that semaglutide-induced weight loss is sustained with continued treatment, without evidence of weight regain or tachyphylaxis. This supports the concept of obesity as a chronic disease requiring ongoing pharmacotherapy, analogous to hypertension or diabetes management.
Related
#research #RCT #semaglutide #evidence-level-I