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 STEP trials, which are testing semaglutide at the higher dose of 2.4 mg/week, specifically for promoting weight loss, regardless of the presence of type 2 diabetes. More recent trials are exploring an even higher dose, of 7.2 mg/week. We also include the cardiovascular outcomes study for the 2.4 mg dose, SELECT. We will update the page as new results become available.
See also:
- A quick guide to the SURPASS and SURMOUNT trials (tirzepatide)
- A quick guide to the PIONEER trials (oral semaglutide)
- A quick guide to the SUSTAIN trials (semaglutide)
- A quick guide to the AWARD trials (dulaglutide)
- A quick guide to the GetGoal trials (lixisenatide)
- A quick guide to the LEAD trials (liraglutide)
- A quick guide to the DURATION trials (exenatide)
STEP 1: Published
Trial population: Obese or overweight people with related comorbidities, but not diabetes | Comparator treatment: Placebo |
The STEP 1 trial involved 1961 participants and was published in The New England Journal of Medicine in early 2021.
The findings revealed an average 14.9% reduction in bodyweight from baseline during 68 weeks of treatment with semaglutide 2.4 mg plus a lifestyle intervention, compared with just a 2.4% reduction in the placebo plus lifestyle intervention group.
In total, 86.4% of the semaglutide group lost at least 5% of their bodyweight, and adverse effects were in line with those expected for the medication class.
Related news stories:
STEP 2: Published
Trial population: Overweight or obese people with type 2 diabetes | Comparator treatments: semaglutide 1.0 mg and placebo |
This trial, published in The Lancet, recruited 1210 participants with type 2 diabetes and overweight or obesity and tested the standard approved 1.0 mg dose versus the higher 2.4 mg dose and matched placebos over 68 weeks.
Average bodyweight reductions were 9.64%, 6.99%, and 3.42% with semaglutide 2.4 mg, 1.0 mg, and placebo, respectively. The higher dose also achieved slightly better glycemic control, reductions in cardiometabolic risk, and improved physical function relative to the standard dose.
Related news story: STEP 2 shows benefits of higher semaglutide dose in type 2 diabetes
STEP 3: Published
Trial population: Overweight or obese people with related comorbidities, but not diabetes | Comparator treatment: Placebo |
The 611 participants of STEP 3 were randomly assigned to receive semaglutide 2.4 mg or placebo in addition to intensive behavioral therapy to support them to adopt a healthier lifestyle.
As reported in JAMA, the average weight reduction after 68 weeks of treatment was 16.0% with semaglutide versus 5.7% with placebo. The co-primary endpoint of at least a 5% reduction in bodyweight was met by 86.6% versus 47.6%.
Related news story: STEP 3: Semaglutide boosts weight loss in intensive behavioral therapy setting
STEP 4: Published
Trial population: Overweight or obese people with related comorbidities, but not diabetes | Comparator treatment: Placebo |
In this trial, the 902 participants all received semaglutide 2.4 mg for the first 20 weeks, after which they were randomly assigned to receive either semaglutide or placebo for the remaining 48 weeks.
The investigators reported in JAMA that participants who continued to take semaglutide after randomization lost an additional 7.9% of their bodyweight, on average, to give a total 17.4% weight loss over the whole trial, whereas those who switched to placebo regained an average 6.9%, giving a total weight loss of 5.0%.
Related news story: STEP 4: Long-term treatment needed for full semaglutide benefit
STEP 5: Published
Trial population: Obese or overweight people with related comorbidities, but not diabetes | Comparator treatment: Placebo |
This trial, published in Nature Medicine, tested the durability of weight loss with semaglutide 2.4 mg versus placebo across a full 2 years of treatment in 304 participants.
Semaglutide resulted in decreasing weight until about week 60, and the weight loss was maintained through week 104, at which point there was an average placebo-corrected weight loss of 12.6 percentage points.
Related news story: STEP 5: Sustained semaglutide treatment maintains weight loss
STEP 6: Published
Trial population: Obese or overweight East Asian people with related comorbidities. | Comparator treatment: Placebo |
This trial, reported in The Lancet Diabetes & Endocrinology, focused on Asian people (n=401), specifically those from Japan and South Korea.
The researchers found significantly greater bodyweight reductions in people given semaglutide 2.4 or 1.7 mg/week versus placebo, at 13.2%, 9.6%, and 2.1%, respectively.
Semaglutide treatment also produced a significant reduction in abdominal visceral fat in a subset of people who underwent computed tomography and a significant reduction in glycated hemoglobin in people (~25%) with type 2 diabetes.
Related news story: STEP 6: Semaglutide addresses ‘pathophysiology of metabolic syndrome’ in Asians
STEP 7: Completed, not yet published
Trial population: Overweight or obese people with or without type 2 diabetes | Comparator treatment: Placebo |
This trial aims to recruit 375 people – with or without type 2 diabetes – largely across China, but also Hong Kong, the Republic of Korea and Brazil. The participants will receive semaglutide 2.4 mg or placebo for 44 weeks.
STEP 8: Published
Trial population: Overweight or obese people with type 2 diabetes | Comparator treatment: Liraglutide, placebo |
STEP 8 compared the weight loss efficacy of semaglutide 2.4 mg against the daily injectable GLP-1 receptor agonist liraglutide at its approved dose for obesity, of 3.0 mg.
The results, published in JAMA, showed a significantly greater average bodyweight reduction of 15.8% with semaglutide, compared with 6.4% with liraglutide. This equated to average 15.3 and 6.8 kg decreases.
Related news story: STEP 8: Semaglutide better than liraglutide at weight-management doses
STEP 9: Active, not recruiting
Trial population: People with obesity and pain due to knee osteoarthritis | Comparator treatment: Placebo |
This trial has enrolled 407 participants and is assessing the co-primary endpoint of weight change and change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score over 68 weeks of treatment.
STEP 10: Active, not recruiting
Trial population: People with obesity and prediabetes | Comparator treatment: Placebo |
This trial is assessing change in glycated hemoglobin, as well as in bodyweight, over 52 weeks in people who have prediabetic blood glucose levels in addition to obesity.
STEP TEENS: Published
Trial population: Adolescents with obesity, or overweight plus related comorbidities | Comparator treatment: Placebo |
As the name suggests, the STEP TEENS trial tested the weight-loss efficacy of semaglutide 2.4 mg in adolescents aged 12–17 years.
Active treatment was associated with a substantial and significant 16.1% reduction in baseline BMI, whereas placebo was associated with a 0.6% increase. Adolescents taking semaglutide also had marked improvements in their lipid profiles, particularly triglycerides.
The findings are published in The New England Journal of Medicine.
Related news story: STEP TEENS: High-dose semaglutide weight loss benefits shown in adolescents
STEP HFpEF DM: Recruiting
Trial population: Overweight or obese people with type 2 diabetes and heart failure with preserved ejection fraction | Comparator treatment: Placebo |
This trial, aiming to enroll 610 participants, is testing whether weight loss with semaglutide is accompanied by improved heart failure symptoms in people with symptomatic heart failure with preserved ejection fraction.
The primary outcome measures will be change in Kansas City Cardiomyopathy Questionnaire clinical summary score, as well as change in bodyweight, over 52 weeks of treatment.
The SELECT trial: Active, not recruiting
Trial population: Overweight or obese people without diabetes but with established cardiovascular disease | Comparator treatment: Placebo |
SELECT is the companion cardiovascular outcomes trial for semaglutide 2.4 mg in people with obesity. This event-driven trial aims to enroll 17,500 participants and follow them up for an estimated 31 to 59 months.
STEP UP: Recruiting
Trial population: People with obesity but without diabetes | Comparator treatment: Semaglutide 2.4 mg, placebo |
In STEP UP, an estimated 1400 participants will be randomly assigned to receive semaglutide at doses of 7.2 or 2.4 mg/week or placebo for 72 weeks.
STEP UP T2D: Recruiting
Trial population: People with obesity and type 2 diabetes | Comparator treatment: Semaglutide 2.4 mg, placebo |
This trial has the same design as STEP UP, but aims to enroll a smaller number (n=500) of participants, all of whom will have type 2 diabetes.
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