STEP 2 is the diabetes counterpart of STEP 1. It also included a 1.0 mg arm, the diabetes dose of the time, which makes it one of the few trials to test two semaglutide doses side by side for weight.
What the trial asked
Whether semaglutide 2.4 mg once weekly is superior to placebo for weight management in adults with type 2 diabetes and a BMI of 27 or higher, with semaglutide 1.0 mg as a second active arm.
Design
Phase 3, double-blind, double-dummy, superiority trial. Randomised 1:1:1 to semaglutide 2.4 mg, semaglutide 1.0 mg or matching placebo, once weekly for 68 weeks, plus lifestyle intervention. Stratified by background glucose-lowering medication and HbA1c. Coprimary endpoints were assessed by intention to treat for 2.4 mg versus placebo. 149 outpatient clinics in 12 countries across Europe, North and South America, the Middle East, South Africa and Asia.
Who was enrolled
Screening ran from June to November 2018; 1595 were screened and 1210 randomised: 404 to 2.4 mg, 403 to 1.0 mg, 403 to placebo. Entry required a BMI of at least 27, HbA1c 7 to 10 percent, and a type 2 diabetes diagnosis at least 180 days before screening. Baseline weight is not stated in the abstract.
Primary endpoint and result
Coprimary endpoints at week 68: percent change in body weight, and weight reduction of at least 5 percent, for 2.4 mg versus placebo.
| Arm | Estimated mean weight change at week 68 |
|---|---|
| Semaglutide 2.4 mg | -9.6% (SE 0.4) |
| Placebo | -3.4% (SE 0.4) |
Estimated treatment difference -6.2 percentage points (95% CI -7.3 to -5.2; p less than 0.0001). At week 68, 267 of 388 (68.8 percent) on 2.4 mg and 107 of 376 (28.5 percent) on placebo had lost at least 5 percent; odds ratio 4.88 (95% CI 3.58 to 6.64; p less than 0.0001).
The abstract does not give the weight change in the 1.0 mg arm, so it is not stated here.
Key secondary results
None are itemised in the abstract beyond the coprimary endpoints.
Adverse events and discontinuation
Adverse events were reported in 353 of 403 (87.6 percent) on 2.4 mg, 329 of 402 (81.8 percent) on 1.0 mg, and 309 of 402 (76.9 percent) on placebo. Gastrointestinal events, mostly mild to moderate: 256 (63.5 percent), 231 (57.5 percent) and 138 (34.3 percent). The abstract does not give discontinuation rates.
Funding and registration
Novo Nordisk. ClinicalTrials.gov NCT03552757.
What this trial does not show
- Same drug, same dose, same duration as STEP 1, roughly two-thirds the effect. The trial documents the difference; it does not explain it.
- The 1.0 mg arm's weight result is in the paper but not the abstract, so this site cannot quote it.
- HbA1c and other glycaemic outcomes are not in the abstract either.
- No cardiovascular or kidney outcomes.
Where the numbers come from
PubMed abstract of the primary paper (PubMed 33667417), fetched 4 September 2026. See the guide on weight-management versus diabetes trials for the recurring pattern across STEP 2, SURMOUNT-2, ATTAIN-2 and REDEFINE 2.
Sources
- Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021;397(10278):971-984. PubMed 33667417 Accessed September 4, 2026.
- ClinicalTrials.gov NCT03552757 Accessed September 4, 2026.
Canonical URL: https://formblendsresearch.com/trials/step-2. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.