THE BOTTOM LINE
In adults with a body mass index of ≥ 30 kg/m2 without diabetes, 2.4 mg of subcutaneous semaglutide weekly with lifestyle intervention led to a sustained, clinically relevant body weight reduction over 68 weeks compared to placebo.
WHY THIS IS IMPORTANT
Obesity is a public health crisis that is increasing in prevalence and can lead to comorbidities such as type 2 diabetes, hypertension, and dyslipidemia.1
Sustaining lifestyle interventions to reduce weight can be challenging for some patients.2
While previous trials on glucagon-like peptide (GLP-1) receptor agonists noted weight loss in patients who had diabetes, the impact of GLP-1 agonists on weight loss in patients without diabetes remained unknown prior to the STEP 1 trial.3
FACTS
Setting
129 sites in 16 countries from 2018 to 2019
Participants
Inclusion criteria: Adults ≥ 18 years old with one or more self-reported unsuccessful dietary efforts to lose weight. Adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with one or more weight-related coexisting conditions (e.g., hypertension, dyslipidemia).
Exclusion criteria: Adults with diabetes, hemoglobin A1C ≥ 6.5%, history of chronic pancreatitis, acute pancreatitis within 180 days, previous surgical obesity treatment, use of antiobesity medication within 90 days
1961 participants randomized 2:1 to intervention versus placebo
Baseline characteristics: 74.1% female, 75.1% white; mean age of 46 years; mean BMI 37.9 kg/m2; 43.7% with prediabetes
Intervention
Intervention: 2.4 mg of once-weekly semaglutide pen injection
Control: placebo pen injection
All participants received individual counseling sessions every 4 weeks to help adhere to lifestyle intervention
Primary Outcomes
Percentage change in body weight from baseline to week 68
Achievement of reduction in body weight of ≥ 5% from baseline to week 68
RESULTS
Participants in the semaglutide group lost 14.9% of their body weight from baseline compared to 2.4% with the placebo group (p < 0.001, see Fig. 1).
Participants in the semaglutide group were more likely to achieve ≥ 5% weight loss (84.6% vs. 31.5%; p < 0.001) with a number needed to treat of 2.
Participants in the semaglutide group had larger improvements from baseline in key secondary outcomes, including waist circumference, BMI, blood pressure, and physical function.
Participants in the semaglutide group were more likely to experience serious adverse events (9.8% vs. 6.4%; p < 0.001), mainly gastrointestinal and hepatobiliary disorders, with a number needed to harm of 29.
Figure 1.
Effect of once-weekly semaglutide as compared with placebo on body weight.
STUDY QUALITY AND APPLICATION TO PATIENTS
The study quality is good (per USPSTF criteria).
As the study included 74.1% women and 75.1% white individuals, and excluded patients with type 2 diabetes, additional research should assess the effects of semaglutide in men and adults of different ethnicities.
The degree to which the weight loss achieved will persist after the 68-week intervention period is also unclear.
The diet and exercise counseling may not be universally available to individuals, and out-of-pocket costs for semaglutide as a weight loss medication may be substantial.4
Head-to-head comparisons of GLP-1 agonists, SGLT-2 inhibitors, and other FDA-approved weight loss medications will be informative.
Declarations
Conflict of Interest
The authors declare that they do not have a conflict of interest.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Rachel S. Chang, Email: Rachel.s.chang@vanderbilt.edu.
Jiun-Ruey Hu, Email: Jiun-ruey.hu@yale.edu.
Hsin-Chieh Yeh, Email: Hyeh1@jhmi.edu.
References
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