STEP 1
Trial question
What is the role of once weekly semaglutide as an adjunct to lifestyle intervention in adults with overweight or obesity?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
74.0% female
26.0% male
N = 1961
1961 patients (1453 female, 508 male).
Inclusion criteria: patients with a BMI of ≥ 30 (or ≥ 27 with ≥ 1 weight-related coexisting condition) who did not have diabetes.
Key exclusion criteria: HbA1c ≥ 6.5%, self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening, previous treatment with glucose-lowering agents or any antiobesity medications within the past 90 days before screening.
Interventions
N=1306 semaglutide (initiated at 0.25 mg SC once weekly for the first 4 weeks and titrated every 4 weeks to the maintenance dose of 2.4 mg once weekly by week 16, plus diet and physical activity counseling).
N=655 placebo (matching placebo once weekly plus diet and physical activity counseling).
Primary outcome
Relative weight reduction at week 68
14.9%
2.4%
14.9 %
11.2 %
7.5 %
3.7 %
0.0 %
Semaglutide
Placebo
Significant
increase ▲
NNT = 8
Significant increase in relative weight reduction at week 68 (14.9% vs. 2.4%; AD 12.4%, 95% CI 11.5 to 13.4).
Secondary outcomes
Significant increase in the percentage of patients achieving a weight reduction of ≥ 10% at week 68 (69.1% vs. 12%; OR 14.7, 95% CI 11.1 to 19.4).
Significant increase in the percentage of patients achieving a reduction in weight by ≥ 15% at week 68 (50.5% vs. 4.9%; OR 19.3, 95% CI 12.9 to 28.8).
Significant increase in absolute weight reduction from baseline to week 68 (15.3 kg vs. 2.6 kg; AD 12.7 kg, 95% CI 11.7 to 13.7).
Safety outcomes
No significant difference in overall adverse events.
Significant differences in serious adverse events (9.8% vs. 6.4%), gastrointestinal disorders (74.2% vs. 47.9%), treatment discontinuation due to gastrointestinal events (4.5% vs. 0.8%).
Conclusion
In patients with a BMI of ≥ 30 (or ≥ 27 with ≥ 1 weight-related coexisting condition) who did not have diabetes, semaglutide was superior to placebo with respect to relative weight reduction at week 68.
Reference
John P H Wilding, Rachel L Batterham, Salvatore Calanna et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002.
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