Efficacy and Safety of Semaglutide 2.4 MG Once-Weekly in Adults With Overweight or Obesity and Type 2 Diabetes (STEP 2)
Bibliographic record
Abstract
Abstract Background: In people with overweight/obesity and type 2 diabetes (T2D), achievement of weight loss can be a challenge. STEP 2 investigated the efficacy and safety of semaglutide 2.4 mg for weight management in adults with overweight/obesity and T2D. Methods: This randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial was conducted at 149 sites across 12 countries (NCT03552757). Adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2, T2D, HbA1c between 7–10% (53–86 mmol/mol), and receiving ≤3 oral glucose-lowering agents were randomized 1:1:1 to once-weekly subcutaneous (s.c.) semaglutide 2.4 mg or 1.0 mg, or placebo, as adjunct to a reduced-calorie diet and increased physical activity for 68 weeks. The co-primary endpoints were percentage change in body weight and proportion of participants achieving weight loss ≥5% for semaglutide 2.4 mg vs placebo. Cardiovascular risk factors, glycemia and safety/tolerability were also assessed. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: 1,210 participants (mean: age 55 years, body weight 99.8 kg, BMI 35.7 kg/m2, HbA1c 8.1%, diabetes duration 8.0 years; 50.9% female) were randomized. Mean body weight change from baseline to week 68 was −9.6% with semaglutide 2.4 mg vs −3.4% with placebo (estimated treatment difference [ETD]: −6.2%; 95% confidence interval [CI]: −7.3, −5.2; p<0.0001) and −7.0% for semaglutide 1.0 mg (ETD for semaglutide 2.4 mg vs 1.0 mg: −2.7%; 95% CI: −3.7, −1.6; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change −10.6% for semaglutide 2.4 mg vs −3.1% for placebo (ETD: −7.6%; 95% CI: −8.6, −6.6; p<0.0001) and 7.6% for semaglutide 1.0 mg (ETD vs semaglutide 2.4 mg: −3.1%; 95% CI: −4.1, −2.1; p<0.0001). Participants on semaglutide 2.4 mg were more likely to achieve weight loss ≥5%, ≥10%, ≥15% and ≥20% vs placebo (68.8% vs 28.5%, 45.6% vs 8.2%, 25.8% vs 3.2% and 13.1% vs 1.6%, respectively; p value for odds ratios <0.0001 for all). Mean change in HbA1c from baseline to week 68 was −1.6% for semaglutide 2.4 mg vs −0.4% for placebo (p<0.0001). Greater improvements with semaglutide 2.4 mg vs placebo were also seen in waist circumference, BMI, systolic blood pressure, fasting plasma glucose, C-reactive protein, and lipids (HDL, VLDL, free fatty acids, and triglycerides) (p<0.05 for all). The most frequent adverse events were gastrointestinal disorders (typically transient and mild-to-moderate), occurring in 57.5%, 63.5% and 34.3% of participants receiving semaglutide 1.0 mg, 2.4 mg and placebo, respectively. Conclusion: Semaglutide 2.4 mg, as adjunct to lifestyle intervention, was efficacious and well tolerated for weight management in adults with overweight or obesity and T2D, providing significantly greater weight loss vs placebo and semaglutide 1.0 mg at week 68.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".