Updated September 2025 At a glance: The STEP trials

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 NCT03548935 Wilding JPH et al. N Engl J Med 2021; 384: 989–1002. 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 cardiometabolic risk and improved physical function than semaglutide 1 mg NCT03552757 Davies M et al. The Lancet 2021; 397: 971–984. 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 NCT03611582 Wadden TA et al. JAMA 2021; 325: 1403–1413. 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 NCT03548987 Rubino D et al. JAMA 2021; 325: 1414–1425. 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 NCT03693430 Garvey WT et al. Nature Medicine 2022; 28: 2083–2091. 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 NCT03811574 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 NCT04251156 Mu Y et al. Lancet Diabetes Endocrinol 2024; 12: 184–195. 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 NCT04074161 Rubino DM et al. JAMA 2022; 327: 138–150. STEP 9 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 13.7% vs 3.2% mean bodyweight reduction from baseline 41.7 point vs 27.5 point mean reduction in WOMAC pain score from baseline Secondary outcome 12.0 point vs 6.5 point mean change in SF-36 physical-function score NCT05064735 Bliddal H et al. New Engl J Med 2024; 391:1573–1583. STEP 10 Published Trial population Obesity, with prediabetes Intervention and comparator Semaglutide 2.4 mg or placebo for 52 weeks Primary outcomes 13.9% vs 2.7% mean bodyweight reduction from baseline 81% (103 of 127) vs 14% (9 or 64) reached normoglycemia NCT05040971 McGowan BM et al. Lancet Diabetes Endocrinol 2024; 12: 631–642. STEP 12 Completed Trial population BMI of ≥24 kg/m2 and <28 kg/m2, at least one weight-related comorbidity, with or without diabetes, or BMI of ≥28 kg/m2 and <30 kg/m2, with or without weight-related comorbidities 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 achieving ≥5% bodyweight reduction from baseline NCT06041217 Study completion May 7 2025 STEP YOUNG Active, not recruiting Trial population Children with a BMI ≥95th percentile and teenagers with a BMI ≥95th percentile or ≥85th percentile with at least one related comorbidity, with or without diabetes Intervention and comparator Semaglutide 2.4 mg vs placebo for 132 weeks Primary outcomes Assessing percentage change in bodyweight from baseline to week 68 NCT05726227 Estimated study completion December 7 2026 STEP TEENS Published Trial population Adolescents, obese or overweight with at least one weight-related comorbidity Intervention and comparator Semaglutide 2.4 mg (or max tolerated dose) vs placebo for 68 weeks Primary outcomes 16.1% vs 0.6% mean bodyweight reduction from baseline NCT04102189 Weghuber D et al. N Engl J Med 2022; 387: 2245–2257. 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 NCT04788511 Kosiborod MN et al. N Engl J Med 2023; 389: 1069–1084. 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 NCT04916470 Kosiborod MN et al. N Engl J Med 2024; doi:10.1056/NEJMoa2313917. STEP UP Published Trial population Obese, no diabetes Intervention and comparator Semaglutide 7.2 mg vs 2.4 mg vs placebo for 72 weeks Primary outcomes 18.7% vs 15.6% vs 3.9% mean bodyweight reduction from baseline 90.7% of participants in the semaglutide 7.2 mg arm vs 36.8% in the placebo arm lost at least 5% of their bodyweight from baseline NCT05646706 Wharton S, et al. Lancet Diabetes Endocrinol 2025; doi:10.1016/S2213-8587(25)00226-8. STEP UP T2D Published 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 13.2% vs 10.4% vs 3.9% mean bodyweight reduction from baseline 86.3% of participants in the semaglutide 7.2 mg arm vs 34.7% in the placebo arm lost at least 5% of their bodyweight from baseline NCT05649137 Lingvay I, et al. Lancet Diabetes Endocrinol 2025; doi:10.1016/S2213-8587(25)00225-6. Provided by Springer Medicine © 2023 Springer Medizin Verlag GmbH, part of the Springer Nature Group

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Updated September 2025 At a glance: The STEP trials

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