Key facts
- Drug / target: semaglutide 2.4 mg once weekly, subcutaneous — a GLP-1 receptor agonist.
- Sponsor: Novo Nordisk.
- Design: randomized (1:1:1), double-blind, double-dummy, placebo-controlled phase 3 superiority trial.
- Comparators: semaglutide 2.4 mg vs semaglutide 1.0 mg (the diabetes-approved dose) vs placebo, all plus lifestyle intervention.
- Population: 1,210 adults with BMI ≥ 27, HbA1c 7–10%, and type 2 diabetes diagnosed ≥ 180 days before screening; recruited from 149 clinics in 12 countries.
- Duration: 68 weeks of treatment.
- Coprimary endpoints: percentage change in bodyweight and achievement of ≥ 5% weight reduction at 68 weeks, semaglutide 2.4 mg vs placebo.
- Headline result: −9.6% (semaglutide 2.4 mg) vs −3.4% (placebo); difference −6.2 percentage points (95% CI −7.3 to −5.2; p<0.0001).
- Registration: NCT03552757 — ClinicalTrials.gov.
- Publication: The Lancet, 2021 — PMID 33667417.
What was the STEP 2 trial?
STEP 2 was a randomized, double-blind, double-dummy, placebo-controlled phase 3 trial that assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg for weight management in adults who had both overweight or obesity and type 2 diabetes. It was sponsored by Novo Nordisk and published in The Lancet in 2021 (PMID 33667417).
What set STEP 2 apart from the rest of the STEP programme was its three-way comparison. Rather than pit semaglutide only against placebo, it also included a semaglutide 1.0 mg arm — the dose already approved for treating type 2 diabetes. That let the trial ask two things at once: is the higher 2.4 mg weight-management dose better than placebo, and how does it sit relative to the familiar diabetes dose. The trial is registered as NCT03552757 on ClinicalTrials.gov.
Weight loss tends to be harder to achieve in people who have type 2 diabetes than in those who do not, which is one reason a dedicated trial in this population was worth running. Where STEP 1 studied semaglutide 2.4 mg in people with obesity but without diabetes, STEP 2 focused squarely on the diabetes population.
Who was in it?
STEP 2 randomly assigned 1,210 adults 1:1:1 to semaglutide 2.4 mg (404 participants), semaglutide 1.0 mg (403 participants), or placebo (403 participants), all analysed by intention to treat. To be eligible, participants needed a body-mass index of at least 27 kg/m², a glycated haemoglobin (HbA1c) of 7 to 10%, and a diagnosis of type 2 diabetes made at least 180 days before screening. Recruitment spanned 149 outpatient clinics across 12 countries in Europe, North America, South America, the Middle East, South Africa and Asia.
Assignment was stratified by background glucose-lowering medication and by HbA1c, and everyone — participants, investigators and outcome assessors — was masked to group allocation. That masking, combined with the double-dummy design in which each arm received matching injections, is what keeps expectations from colouring the results.
What did participants receive?
Each participant received once-weekly subcutaneous injections for 68 weeks: semaglutide 2.4 mg, semaglutide 1.0 mg, or a visually matching placebo, layered on top of a lifestyle intervention that included a reduced-calorie diet and increased physical activity. Because the study was double-dummy, participants in every arm took injections on the same schedule, so no one could infer their assignment from how the treatment was delivered.
Describing the assigned regimen is reporting what the trial did — it is not a dosing instruction. Semaglutide is prescription-only, and the dose any individual might use is a clinical decision, not something to infer from a trial protocol. The 2.4 mg weekly maintenance dose is the one approved for chronic weight management, marketed as Wegovy; the underlying molecule is covered in our semaglutide research summary.
Primary results
STEP 2 had two coprimary endpoints, both comparing semaglutide 2.4 mg with placebo at week 68: the percentage change in bodyweight, and the proportion of participants achieving a weight reduction of at least 5%.
The estimated change in mean bodyweight from baseline to week 68 was −9.6% (standard error 0.4) with semaglutide 2.4 mg, compared with −3.4% (0.4) with placebo. The estimated treatment difference for semaglutide 2.4 mg versus placebo was −6.2 percentage points (95% CI −7.3 to −5.2; p<0.0001). On the categorical endpoint, more participants on semaglutide 2.4 mg than on placebo reached at least 5% weight loss: 267 of 388 (68.8%) versus 107 of 376 (28.5%), an odds ratio of 4.88 (95% CI 3.58 to 6.64; p<0.0001).
| Coprimary endpoint at week 68 | Semaglutide 2.4 mg | Placebo | Effect |
|---|---|---|---|
| Estimated mean bodyweight change from baseline | −9.6% (SE 0.4) | −3.4% (SE 0.4) | Difference −6.2 pp (95% CI −7.3 to −5.2); p<0.0001 |
| Achieved ≥ 5% weight reduction | 267 / 388 (68.8%) | 107 / 376 (28.5%) | OR 4.88 (95% CI 3.58 to 6.64); p<0.0001 |
The published abstract reports the coprimary comparison as semaglutide 2.4 mg versus placebo; it does not attach a separate bodyweight percentage to the 1.0 mg arm, so this page does not either. The overall conclusion the authors drew is that, in adults with overweight or obesity and type 2 diabetes, semaglutide 2.4 mg once a week achieved a superior and clinically meaningful decrease in bodyweight compared with placebo.
Safety and side effects reported
Adverse events were more frequent in both semaglutide arms than with placebo. Any adverse event was reported in 353 of 403 participants (87.6%) on semaglutide 2.4 mg, 329 of 402 (81.8%) on semaglutide 1.0 mg, and 309 of 402 (76.9%) on placebo.
Gastrointestinal adverse events — the class most associated with GLP-1 receptor agonists — were mostly mild to moderate and were reported in 256 of 403 participants (63.5%) on semaglutide 2.4 mg, 231 of 402 (57.5%) on semaglutide 1.0 mg, and 138 of 402 (34.3%) on placebo. This page reports only the aggregate figures stated in the peer-reviewed record rather than assigning rates to individual symptoms. For a broader picture of the side effects seen across the GLP-1 class, see the relevant sections of our guide to peptides for weight loss.
Limitations and what it does not prove
STEP 2 is a strong trial, but it has boundaries worth keeping in view:
- It studied a specific population. Everyone enrolled had type 2 diabetes, a BMI of at least 27, and an HbA1c of 7–10%. The result applies most directly to people like those enrolled and should not be generalised to people without diabetes, where a separate trial (STEP 1) applies.
- It measured weight, not long-term outcomes. The coprimary endpoints were bodyweight change and the proportion reaching 5% loss at 68 weeks. It was not designed to measure cardiovascular events or long-term diabetes complications.
- It reflects continued treatment plus lifestyle support. Participants took the drug for 68 weeks alongside a structured diet and activity programme. It does not describe what happens after treatment stops.
- The abstract-level figures are for the 2.4 mg versus placebo comparison. The headline numbers quoted here are for that contrast; the 1.0 mg arm was included for context rather than as the primary comparison.
None of this diminishes the finding. It keeps it the right size: robust evidence of weight reduction with semaglutide 2.4 mg in adults who have type 2 diabetes and excess weight.
Why the STEP 2 trial matters
People with type 2 diabetes have historically lost less weight than people without diabetes on the same interventions, so a dedicated, adequately powered trial mattered. STEP 2 provided it, showing that the 2.4 mg weight-management dose produced meaningfully more weight loss than placebo in exactly the group where weight loss is hardest to achieve. It rounded out the evidence base that supported semaglutide 2.4 mg as a chronic weight-management therapy across populations with and without diabetes.
STEP 2 also sits within a larger map of GLP-1 based evidence. For how semaglutide performs for weight loss in people without diabetes, see STEP 1; for the drug itself, the semaglutide research summary; and for the wider landscape of which weight-loss peptides carry this caliber of evidence, our pillar guide on peptides for weight loss and the full list of research articles.
Frequently asked questions
What did the STEP 2 trial show?
STEP 2 showed that once-weekly semaglutide 2.4 mg produced greater weight loss than placebo in adults with overweight or obesity and type 2 diabetes. The estimated change in mean bodyweight from baseline to week 68 was -9.6% with semaglutide 2.4 mg versus -3.4% with placebo, an estimated treatment difference of -6.2 percentage points (95% CI -7.3 to -5.2; p<0.0001). It was a phase 3 superiority trial funded by Novo Nordisk and published in the Lancet in 2021.
Who was enrolled in the STEP 2 trial?
STEP 2 enrolled 1,210 adults with a body-mass index of at least 27 kg/m2 and a glycated haemoglobin of 7 to 10% who had been diagnosed with type 2 diabetes at least 180 days before screening. Participants were recruited from 149 outpatient clinics across 12 countries and randomly assigned 1:1:1 to semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo, each with a lifestyle intervention.
How much weight did people lose in STEP 2?
The estimated mean bodyweight change from baseline to week 68 was -9.6% with semaglutide 2.4 mg compared with -3.4% with placebo. More participants on semaglutide 2.4 mg than on placebo reached a weight reduction of at least 5%: 267 of 388 (68.8%) versus 107 of 376 (28.5%), an odds ratio of 4.88 (95% CI 3.58 to 6.64; p<0.0001).
What doses of semaglutide did STEP 2 compare?
STEP 2 compared three once-weekly subcutaneous arms: semaglutide 2.4 mg, semaglutide 1.0 mg (the dose approved for type 2 diabetes treatment), and a matching placebo, each given for 68 weeks alongside a lifestyle intervention. This is reporting what the trial administered, not a dosing recommendation; any use of semaglutide is a prescription decision made with a clinician.
What side effects were reported in STEP 2?
Adverse events were more frequent with semaglutide than placebo: they occurred in 87.6% of the semaglutide 2.4 mg group, 81.8% of the 1.0 mg group, and 76.9% of the placebo group. Gastrointestinal adverse events, mostly mild to moderate, were reported in 63.5% of the 2.4 mg group, 57.5% of the 1.0 mg group, and 34.3% of the placebo group.
How is STEP 2 different from STEP 1?
STEP 1 studied semaglutide 2.4 mg for weight management in adults with overweight or obesity who did not have diabetes, while STEP 2 studied the same weekly dose specifically in adults who did have type 2 diabetes. Weight loss in people with diabetes is typically more modest than in people without it, which is one reason the two trials are reported separately.
Sources
This summary traces to the peer-reviewed publication and trial registration:
- Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2) — The Lancet, 2021; PubMed 33667417.
- STEP 2 (semaglutide in overweight/obesity and type 2 diabetes) — ClinicalTrials.gov NCT03552757.
- Drug reference record: semaglutide.