STEP trial programme (revision 7)
Old revision·09:09, 29 Aug 2024·DataTableDunja
| STEP trial programme | |
|---|---|
| Full name | Semaglutide Treatment Effect in People with obesity |
| Drug | Semaglutide 2.4 mg weekly |
| Indication | Chronic weight management |
| Principal duration | 68 weeks |
| Topic infobox · conventions | |
The STEP trial programme is the series of phase 3 randomised trials that established weekly semaglutide 2.4 mg for chronic weight management. Its constituent trials differ in population — with and without type 2 diabetes, with and without intensive behavioural therapy, and in the comparison made — and each addresses a distinct question.[1]
STEP 1, the largest and most cited, randomised 1,961 adults with obesity and without diabetes to semaglutide 2.4 mg or placebo for 68 weeks, both arms receiving lifestyle intervention. Mean weight change was −14.9% on active treatment and −2.4% on placebo.[1]
The placebo arm is essential to interpreting that figure. Both arms received counselling on diet and physical activity, so the −2.4% is not a no-treatment baseline, and the placebo-adjusted difference of about 12.4 percentage points is the quantity attributable to the drug.[2]
The constituent trials
[edit]| Trial | Population | Comparison | Weight change, active vs comparator |
|---|---|---|---|
| STEP 1 | Obesity, no diabetes | Placebo | −14.9% vs −2.4% |
| STEP 2 | Obesity with type 2 diabetes | Placebo and 1.0 mg | −9.6% vs −3.4% |
| STEP 3 | Obesity, intensive behavioural therapy | Placebo | −16.0% vs −5.7% |
| STEP 4 | Randomised withdrawal after run-in | Continue vs switch to placebo | Continued loss vs regain |
| STEP 8 | Obesity, no diabetes | Liraglutide 3.0 mg | −15.8% vs −6.4% |
STEP 2 illustrates a consistent finding in this field: weight response is attenuated in people with type 2 diabetes, for reasons that are not established. STEP 3 shows that intensive behavioural support raises both arms rather than only the placebo arm.[2]
STEP 4 is the informative one for discontinuation. Participants who reached the maintenance dose during a run-in were randomised either to continue or to switch to placebo; the switched group regained weight steadily thereafter. See Weight regain after discontinuation.[3]
References
- ^ a b Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." New England Journal of Medicine 384(11):989–1002 (2021). DOI:10.1056/NEJMoa2032183. PMID 33567185.
- ^ a b Davies M, Færch L, Jeppesen OK, et al. "Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2)." The Lancet 397(10278):971–984 (2021). PMID 33667417.
- ^ Rubino D, Abrahamsson N, Davies M, et al. "Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance (STEP 4)." JAMA 325(14):1414–1425 (2021). PMID 33755728.