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.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled phase 3 clinical trial
PubMed 33667417 · doi:10.1016/S0140-6736(21)00213-0
What was done
In a double-blind, double-dummy, phase 3 randomized controlled trial across 149 outpatient clinics in 12 countries, 1,210 adults with body mass index ≥27 kg/m², glycated hemoglobin (HbA1c) 7–10%, and type 2 diabetes were randomized 1:1:1 to receive once-weekly subcutaneous semaglutide 2.4 mg (n=404), semaglutide 1.0 mg (n=403), or matched placebo (n=403) for 68 weeks in addition to a lifestyle intervention. Coprimary endpoints were percentage change in body weight and the proportion achieving ≥5% weight loss at week 68 for semaglutide 2.4 mg versus placebo, evaluated on an intention-to-treat basis.
What was found
Estimated mean body weight change at week 68 was -9.6% (SE 0.4) with semaglutide 2.4 mg compared with -3.4% (0.4) with placebo, yielding an estimated treatment difference of -6.2 percentage points (95% CI -7.3 to -5.2; p<0.0001). Significantly more participants in the semaglutide 2.4 mg group achieved ≥5% weight reduction than with placebo (68.8% [267/388] vs 28.5% [107/376]; odds ratio 4.88, 95% CI 3.58 to 6.64; p<0.0001). Adverse events occurred in 87.6% of patients on 2.4 mg, 81.8% on 1.0 mg, and 76.9% on placebo, predominantly driven by mild-to-moderate gastrointestinal events (63.5% with 2.4 mg vs 57.5% with 1.0 mg and 34.3% with placebo).
Why it matters
This trial confirms that once-weekly semaglutide 2.4 mg achieves clinically meaningful weight reduction in adults with type 2 diabetes and excess weight, a population in which weight reduction is typically harder to achieve than in individuals without diabetes.
Limits
Trial duration was limited to 68 weeks, providing no data on long-term weight maintenance or outcomes after drug cessation. Gastrointestinal side effects were common in the active treatment arms. The study population was restricted to patients with baseline HbA1c between 7% and 10%, limiting direct applicability to individuals with tighter or poorer glycemic control.
Cited by
- contradicts In clinical trials, diabetic patients on GLP-1 drugs only lose 3 to 4 pounds on average, whereas non-diabetic individuals with obesity lose 40 to 80 pounds.