Semaglutide Treatment Effect in People With Obesity - STEP 1

Contribution To Literature:

The STEP 1 trial showed that once-weekly semaglutide was superior to placebo at improving weight loss.


The goal of the trial was to evaluate semaglutide compared with placebo among patients with obesity. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue approved for treatment of diabetes and to reduce the risk of cardiovascular events among individuals with diabetes and cardiovascular disease.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Double-blind

Patients with obesity were randomized to semaglutide 2.4 mg subcutaneous once-weekly (n = 1,306) versus placebo (n = 655) for 68 weeks. All participants received lifestyle intervention.

  • Total number of enrollees: 1,961
  • Duration of follow-up: 68 weeks
  • Mean patient age: 46 years
  • Percentage female: 73%
  • Percentage with pre-diabetes: 45%

Inclusion criteria:

  • Obese adults: Body mass index (BMI) ≥30 kg/m2
  • Overweight adults: BMI ≥27 kg/m2 with hypertension, hyperlipidemia, obstructive sleep apnea, or cardiovascular disease

Exclusion criteria:

  • Diabetes or glycated hemoglobin ≥6.5%
  • History of chronic pancreatitis or acute pancreatitis within 180 days of enrollment
  • Previous surgical obesity treatment
  • Use of anti-obesity medication within 90 days of enrollment

Principal Findings:

The co-primary outcome, mean change in body weight from baseline to 68 weeks, was −14.9% in the semaglutide group compared with −2.4% in the placebo group (p < 0.001).

The co-primary outcome, weight loss of 5%, was −86.4% in the semaglutide group compared with −31.5% in the placebo group (p < 0.001).

Secondary outcomes:

  • Adverse events: 89.7% of the semaglutide group compared with 86.4% of the placebo group
  • Serious adverse events: 9.8% of the semaglutide group compared with 6.4% of the placebo group
  • Discontinuation of study drug due to gastrointestinal events: 4.5% of the semaglutide group compared with 0.8% of the placebo group


Among obese patients, the GLP-1 analogue semaglutide plus lifestyle intervention was superior to placebo plus lifestyle intervention at improving weight loss. Semaglutide was associated with a mean change in body weight from baseline to 68 weeks of βˆ’14.9% compared with βˆ’2.4% in the placebo group. Semaglutide was also associated with a significantly greater proportion of participants achieving weight loss of ≥5% compared with placebo. Semaglutide was well-tolerated with similar frequency of adverse events and serious adverse events between treatment arms. More participants in the semaglutide group had to discontinue study drug due to gastrointestinal events. The once-weekly dosing of semaglutide may improve medication adherence.


Wilding JP, Batterham RL, Calanna S, et al., on behalf of the STEP 1 Study Group. Once-Weekly Semaglutide in Adults With Overweight or Obesity. N Engl J Med 2021;Feb 10:[Epub ahead of print].

Editorial: Ingelfinger JR, Rosen CJ. STEP 1 for Effective Weight Control β€” Another First Step? N Engl J Med 2021;Feb 10:[Epub ahead of print].

Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertension, Sleep Apnea

Keywords: Body Mass Index, Diabetes Mellitus, Glucagon-Like Peptide 1, Hyperlipidemias, Hypertension, Hypoglycemic Agents, Life Style, Medication Adherence, Metabolic Syndrome, Obesity, Overweight, Prediabetic State, Primary Prevention, Sleep Apnea, Obstructive, Weight Loss

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