Semaglutide is a weekly injectable glucagon-like peptide (GLP)-1 receptor agonist currently approved for the treatment of people with type 2 diabetes at weekly doses of up to 1.0 mg.
Here we round up the phase 3 STEP trials, which are testing semaglutide at doses escalated to 2.4 mg/week or higher, specifically for weight loss, regardless of the presence of type 2 diabetes. The intervention and comparator arms of all trials included lifestyle intervention, with advice given on adopting a healthy diet and physical exercise.
The drug manufacturer Novo Nordisk is the main sponsor of all the STEP trials.
STEP 1 | Published |
Trial population | Obese or overweight, related comorbidities, no diabetes |
Intervention and comparator | Semaglutide 2.4 mg or placebo for 68 weeks |
Primary outcomes | 14.9% vs 2.4% average bodyweight reduction from baseline 86.5% of the semaglutide group lost at least 5% of their bodyweight |
STEP 2 | Published |
Trial population | Obesity and overweight, type 2 diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs 1.0 mg vs matched placebo for 68 weeks |
Primary outcomes | 9.64% vs 6.99% vs 3.43% average bodyweight reduction from baseline Semaglutide 2.4 mg produced slightly better glycemic control, reductions in |
STEP 3 | Published |
Trial population | Obesity and overweight, related comorbidities, no diabetes |
Intervention and comparator | Intensive behavioral therapy plus semaglutide 2.4 mg or placebo for 68 weeks |
Primary outcomes | 16% vs 5.7% average bodyweight reduction from baseline 86.6% vs 47.6% lost at least 5% of their bodyweight |
STEP 4 | Published |
Trial population | Obesity and overweight, related comorbidities, no diabetes |
Intervention and comparator | Semaglutide 2.4 mg for 20 weeks then semaglutide 2.4 mg vs placebo for 48 weeks |
Primary outcomes | 17.4% vs 5.0% average bodyweight reduction from baseline Average 7.9% additional weight loss for semaglutide vs 6.95% weight gain for placebo |
STEP 5 | Published |
Trial population | Obesity and overweight, related comorbidities, no diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 2 years |
Primary outcomes | Average placebo-corrected weight loss of 12.6 percentage points at 104 weeks |
STEP 6 | Published |
Trial population | East Asian, obesity or overweight, related comorbidities, with or without diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs 1.7 mg vs placebo for 68 weeks |
Primary outcomes | 13.2% vs 9.6% vs 2.1% average bodyweight reduction from baseline |
Kadowaki T et al. Lancet Diabetes Endocrinol 2022; 10: 193–206. |
STEP 7 | Published |
Trial population | East Asian, obesity or overweight, with or without type 2 diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 44 weeks |
Primary outcomes | 12.1% vs 3.6% mean reduction in bodyweight from baseline 85% vs 31% of participants lost at least 5% of their bodyweight |
STEP 8 | Published |
Trial population | Obesity and overweight, with type 2 diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs daily injectable liraglutide 3.0 mg vs placebo for 68 weeks |
Primary outcomes | 15.8% vs 6.4% average bodyweight reduction from baseline |
STEP 9 | Completed, not published |
Trial population | Obesity, pain due to knee osteoarthritis, no diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 68 weeks |
Primary outcomes | Assessing change in bodyweight and change in WOMAC pain score |
STEP 10 | Completed, not published |
Trial population | Obesity, with prediabetes |
Intervention and comparator | Semaglutide 2.4 mg or placebo for 52 weeks |
Primary outcomes | Assessing percentage change in bodyweight and change to normoglycemia |
STEP 12 | Active, not recruiting |
Trial population | BMI of ≥24 kg/m2 and <28 kg/m2, at least one weight-related comorbidity, with or without |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 44 weeks |
Primary outcomes | Assessing change in bodyweight from baseline and the number of participants |
STEP YOUNG | Active, recruiting |
Trial population | Children with a BMI ≥95th percentile and teenagers with a BMI ≥95th percentile or |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 132 weeks |
Primary outcomes | Assessing percentage change in bodyweight from baseline to week 68 |
STEP TEENS | Published |
Trial population | Adolescents, obese or overweight, with related comorbidities |
Intervention and comparator | Semaglutide 2.4 mg or max tolerated dose vs placebo for 68 weeks |
Primary outcomes | Assessing percentage change in bodyweight from baseline |
STEP-HFpEF | Published |
Trial population | Obese or overweight, with heart failure with preserved ejection fraction, no type 2 diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 52 weeks |
Primary outcomes | 16.6 point vs 8.7 point mean change in KCCQ clinical summary score 13.3% vs 2.6% mean bodyweight reduction from baseline |
STEP-HFpEF DM | Published |
Trial population | Obese or overweight, with heart failure with preserved ejection fraction, with type 2 diabetes |
Intervention and comparator | Semaglutide 2.4 mg vs placebo for 52 weeks |
Primary outcomes | 13.7 point vs 6.4 point mean change in KCCQ clinical summary score 9.8% vs 3.4% mean bodyweight reduction from baseline |
Kosiborod MN et al. N Engl J Med 2024; doi:10.1056/NEJMoa2313917. |
STEP UP | Active, not recruiting |
Trial population | Obese, no diabetes |
Intervention and comparator | Semaglutide 7.2 mg vs 2.4 mg vs placebo for 72 weeks |
Primary outcomes | Assessing percentage change in bodyweight from baseline and the number of participants |
STEP UP T2D | Active, not recruiting |
Trial population | Obese, with type 2 diabetes |
Intervention and comparator | Semaglutide 7.2 mg vs 2.4 mg vs placebo for 72 weeks |
Primary outcomes | Assessing percentage change in bodyweight from baseline and the number of participants |
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