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/m 2 . 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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.015 | 0.033 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.026 | 0.033 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".