Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials
- Design
- Meta-analysis · 4567 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with obesity/overweight.
- Could weight loss explain it?
- Not applicableThe main outcome is weight loss itself, so whether weight loss explains it is not a meaningful question; the abstract does not test whether the gastrointestinal side effects relate to weight loss or reduced intake.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 5 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In 8 trials (4,567 people without diabetes), semaglutide lowered weight about 10% more than placebo, with larger falls in BMI and waist size, and improved blood pressure, C-reactive protein and lipids, but caused more side effects, mainly gastrointestinal.
What the study reported
- Drugs
- Semaglutide
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- More adverse effects than placebo, mainly gastrointestinal.
- Limitations
- Not extracted
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- excluded (no diabetes)
- Sample size
- 4567
Study quality details
- Study design
- Meta-analysis
- Sample size
- 4567
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI: -11
- Risk of bias
- not assessed (auto)
- Peer review status
- yes
How far the review's own results can be trusted
This record is a systematic review, so it is appraised with AMSTAR 2, which rates how far the review's own pooled results can be trusted. It does not grade the trials inside the review; those are appraised one by one.
On this scale High is the best rating. The levels run High, Moderate, Low, Critically low: Critically low confidence in the review is the worst rating a review can receive, and means it should not be relied on for an accurate summary. That is the opposite direction to the risk-of-bias scale used for single trials, where High is the worst.
Critically low confidence in the review · AMSTAR 2 · AI: two passes agreed (item splits settled by owner ruling)
Why: 5 critical items fail: review methods set out in a protocol before the review began; comprehensive literature search; list of excluded studies, with reasons; appropriate methods for combining results; risk of bias taken into account when interpreting the results.
What it is used for here: Used only to find trials. A review at this level does not supply a pooled result to any outcome in this collection; the trials it lists are appraised on their own.
| Item | Answer |
|---|---|
| 1 Research question and inclusion criteria include the PICO components | Yes |
| 2 · critical Review methods set out in a protocol before the review began | No — a critical flaw |
| 3 Choice of included study designs explained | No |
| 4 · critical Comprehensive literature search | No — a critical flaw |
| 5 Study selection done by two reviewers independently | No |
| 6 Data extraction done by two reviewers independently | Yes |
| 7 · critical List of excluded studies, with reasons | No — a critical flaw |
| 8 Included studies described in adequate detail | Partial Yes |
| 9 · critical Satisfactory technique for assessing risk of bias in the included studies | Yes |
| 10 Funding of the included studies reported | No |
| 11 · critical Appropriate methods for combining results | No — a critical flaw |
| 12 Effect of risk of bias on the pooled results assessed | No |
| 13 · critical Risk of bias taken into account when interpreting the results | No — a critical flaw |
| 14 Differences between study results explained and discussed | Yes |
| 15 · critical Publication bias investigated and its likely impact discussed | Yes |
| 16 Review authors' conflicts of interest and funding reported | Yes |
Where the two reviewers differed: item 11 (appropriate methods for combining results): one read Yes, the other No; settled at No by a recorded ruling; item 15 (publication bias investigated and its likely impact discussed): one read No, the other Yes; settled at Yes by a recorded ruling.
Two reviewers assessed the review independently against a written guide (AMSTAR 2 guide, version 1.1), from the full text and retrieved supplements, 2026-10-05.
Funding and conflicts
- Funding
- National Key Research and Development Program of China (2017YFC0909900), per the full text
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
The source, as retrieved
Abstract
Objectives: This study aims to explore the weight loss effect and safety of semaglutide as a conventional anti-obesity drug systematically in obese or overweight patients without diabetes. Methods: The randomized controlled trials (RCTs) of semaglutide in obese or overweight patients without diabetes were retrieved from PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov from database inception until 2 May 2022. Data extraction and quality assessment of studies meeting the inclusion criteria were performed, and statistical analysis was conducted by Review Manager 5.3 and Stata 14. Results: Eight studies involving 4,567 patients were enrolled in the meta-analysis. Compared with placebo, semaglutide induced a significant body weight loss (MD: -10.09%; 95% CI: -11.84 to -8.33; p ˂ 0.00001), elicited a larger reduction in body mass index (MD: -3.71 kg/m2; 95% CI: -4.33 to -3.09; p ˂ 0.00001) and waist circumference (MD: -8.28 cm; 95% CI: -9.51 to -7.04; p ˂ 0.00001), achieved weight loss of more than 5, 10, 15, and 20% with a higher proportion of participants. Semaglutide exhibited a positive effect on blood pressure, C-reactive protein, and lipid profiles, expressed more adverse effects than placebo, mainly gastrointestinal reactions. The results were stable and reliable with dose-dependence. Conclusion: Semaglutide indicated a significant weight loss with an acceptable safety for obese or overweight patients without diabetes.