Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Bibliographic record
Abstract
Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss among individuals without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss among individuals with overweight/obesity and without diabetes. MEDLINE, Embase, and the Cochrane Libraries were systematically searched to identify randomized controlled trials (RCTs) that randomized participants with overweight/obesity but without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo with follow-up of at least 68 weeks. The primary outcome was change in relative body weight from baseline to longest follow-up. Random-effects models with inverse variance weighting were used to estimate weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 RCTs (n=3,087) were included. Of the 3 trials which provided BMI by category (n=2,783), 94.0% of participants had a baseline BMI ≥30 kg/m2. Compared to placebo, use of semaglutide was associated with substantial decreases in long-term relative (WMD: -12.1%; 95% CI -13.5, -10.7) and absolute body weight (WMD: -12.3 kg; 95% CI -13.6, -11.0). At longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared to 2.2% with placebo (RR: 15.08; 95% CI 9.31, 24.43). The risk of gastrointestinal adverse events was higher among semaglutide participants than placebo (RR: 1:47; 95% CI 1.28, 1.68); however, the majority of these events were transient, mild-to-moderate in severity, and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss among individuals with overweight/obesity and without diabetes.
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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 | 0.016 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.089 | 0.012 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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; both teacher heads agree on what is shown here.
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".