Phase 3 — Semaglutide 2.4 mg (Wegovy)
STEP 2: trial summary, limitations and UK relevance
STEP 2 evaluated semaglutide 2.4 mg in adults with type 2 diabetes and overweight or obesity, a population in which incretin-driven weight reduction is typically blunted relative to non-diabetic cohorts. Semaglutide 2.4 mg produced greater mean body-weight reduction than both placebo and the lower semaglutide 1.0 mg dose over 68 weeks. The magnitude of weight reduction reported in STEP 2 was smaller than in the non-diabetic STEP 1 cohort, consistent with the broader pattern that people with type 2 diabetes tend to lose proportionally less weight on GLP-1 receptor agonist therapy. Readers should consult the primary Lancet 2021 publication for exact reported figures.
Key findings
STEP 2 evaluated semaglutide 2.4 mg in adults with type 2 diabetes and overweight or obesity, a population in which incretin-driven weight reduction is typically blunted relative to non-diabetic cohorts. Semaglutide 2.4 mg produced greater mean body-weight reduction than both placebo and the lower semaglutide 1.0 mg dose over 68 weeks. The magnitude of weight reduction reported in STEP 2 was smaller than in the non-diabetic STEP 1 cohort, consistent with the broader pattern that people with type 2 diabetes tend to lose proportionally less weight on GLP-1 receptor agonist therapy. Readers should consult the primary Lancet 2021 publication for exact reported figures.
Safety summary
GI adverse events were the most frequently reported tolerability signal across all arms, with a broadly similar pattern between the two active doses. Hypoglycaemia occurred more often in participants using concomitant sulfonylureas or insulin, a class-recognised interaction rather than a semaglutide-specific finding.
Limitations
- T2D-specific population — weight-reduction magnitude is not directly generalisable to non-diabetic obesity (see STEP 1).
- 68-week duration cannot establish long-term durability, cardiovascular outcomes, or safety after discontinuation.
- Active low-dose (1.0 mg) comparator arm complicates simple placebo-only interpretation of some secondary endpoints.
UK relevance
Supports MHRA/NICE consideration of semaglutide 2.4 mg (Wegovy) for weight management in UK adults who have type 2 diabetes alongside overweight or obesity, a common NHS referral profile.
- Does not establish the same magnitude of weight reduction reported in non-diabetic populations (see STEP 1).
- Does not establish cardiovascular outcome benefit (see SELECT and SUSTAIN-6 for separate outcome-trial evidence).
- Does not prove durability of weight reduction after treatment discontinuation.
Frequently asked questions
How does STEP 2 differ from STEP 1?
STEP 1 enrolled adults with overweight or obesity without type 2 diabetes, while STEP 2 enrolled adults with type 2 diabetes alongside overweight or obesity. STEP 2 reported a smaller magnitude of weight reduction than STEP 1, consistent with the broader pattern that people with type 2 diabetes tend to lose proportionally less weight on GLP-1 receptor agonist therapy.
Why did STEP 2 include a semaglutide 1.0 mg comparator arm?
Semaglutide 1.0 mg is the licensed glycaemic-control dose for type 2 diabetes (as in the Ozempic label). Including it as an active comparator allowed STEP 2 to show that the higher 2.4 mg weight-management dose produced greater body-weight reduction than the standard diabetes dose, not only versus placebo.
What does STEP 2 mean for NHS patients with type 2 diabetes and obesity?
STEP 2 is part of the evidence base supporting MHRA licensing and NICE consideration of semaglutide 2.4 mg (Wegovy) for weight management in adults who have both type 2 diabetes and overweight or obesity — a common presentation in NHS weight-management and diabetes pathways.
Does STEP 2 establish cardiovascular benefit?
No. STEP 2 measured body-weight change as its primary endpoint. Cardiovascular outcome benefit for semaglutide is established separately by the SELECT trial (non-diabetic obesity) and SUSTAIN-6 (type 2 diabetes).
Related peptide profiles
Related trials
Related conditions
Related mechanisms
Related safety signals
Sources are tagged by class. Regulatory documents, peer-reviewed publications and trial registry records are preferred. Manufacturer disclosures and conference material are accepted where peer-reviewed publication is not yet available; preprints are flagged.
- Peer-reviewed publicationDavies M et al., Semaglutide 2.4 mg once a week in adults with overweight or obesity and type 2 diabetes (STEP 2). Lancet 2021.
- Trial registry recordClinicalTrials.gov NCT03552757