Effects of subcutaneous semaglutide on weight loss and inflammatory markers in adults with overweight or obesity without diabetes: a systematic review and meta-analysis
- Design
- Meta-analysis · 6239 participants · Biomarker 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?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 4 · 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.
Across nine placebo-controlled trials (6,239 adults with overweight or obesity and no diabetes), semaglutide reduced body weight by about 12%, waist size by 9.4 cm and CRP by 41% compared with placebo; serious adverse events did not differ significantly (RR 1.12).
What the study reported
- Drugs
- Semaglutide
- Dose
- 2.4 mg in most trials; 7.2 mg in STEP UP
- Route
- subcutaneous
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- excluded (no diabetes)
- Sample size
- 6239
Study quality details
- Study design
- Meta-analysis
- Sample size
- 6239
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- not stated
- Outcome type
- biomarker
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI -13
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- 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: 3 critical items fail: comprehensive literature search; list of excluded studies, with reasons; publication bias investigated and its likely impact discussed.
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 | Partial Yes |
| 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 | Yes |
| 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 | Yes |
| 12 Effect of risk of bias on the pooled results assessed | No |
| 13 · critical Risk of bias taken into account when interpreting the results | Yes |
| 14 Differences between study results explained and discussed | Yes |
| 15 · critical Publication bias investigated and its likely impact discussed | No — a critical flaw |
| 16 Review authors' conflicts of interest and funding reported | Yes |
Where the two reviewers differed: item 3 (choice of included study designs explained): one read Yes, the other No; settled at No 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
- No funding to the authors; editorial assistance was paid through a Novo Nordisk S.p.A. unconditional grant.
- Industry funded
- Unclear
- Manufacturer
- Novo Nordisk, Lilly
- Sponsor role
- Novo Nordisk was not involved in the data analysis; the authors are fully responsible for the contents and conclusions (per full text).
- Author conflicts
- Competing interests: AM was the recipient of a research fellowship funded by Novo Nordisk at the University of Catania during 2023–2024 and received a one-time honorarium from Novo Nordisk in 2023 for participation as faculty in a one-day educational course. LF has acted as a consultant and speaker for Lilly and Novo-Nordisk and has received a grant from Novo Nordisk. All other authors declare no conflicts of interest.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk
Funding is shown on every study and never used to score it.
The source, as retrieved
Abstract
[BACKGROUND/OBJECTIVES] Obesity is a chronic, relapsing disease associated with multiple serious comorbidities. Semaglutide has emerged as an effective pharmacological option for obesity management, owing to its substantial effects on weight loss, cardiometabolic risk factors, and patient-reported outcomes. This systematic review and meta-analysis evaluated the efficacy and safety of subcutaneous semaglutide for weight management in adults with overweight or obesity without diabetes. [METHODS] Randomized controlled trials comparing subcutaneous semaglutide with placebo in adults with overweight or obesity without diabetes were identified through systematic searches of PubMed, the Cochrane Library, and ClinicalTrials.gov. Outcomes included changes in body weight, waist circumference, C-reactive protein (CRP) and serious adverse events (SAEs). A quality assessment and meta-analysis were performed using REVMAN 10.1.1 software. [RESULTS] Across nine trials including 6 239 participants, subcutaneous semaglutide significantly reduced percentage body weight from baseline (mean difference [MD] -12.04%, 95% CI -13.08 to -11.00), waist circumference (MD -9.36 cm, 95% CI -10.27 to -8.45), and CRP (MD -40.90%, 95% CI -46.37 to -35.42) versus placebo (all p < 0.00001). The risk of SAEs did not differ significantly between semaglutide and placebo (risk ratio [RR] 1.12, 95% CI 0.76 to 1.65; p = 0.55). [CONCLUSIONS] Subcutaneous semaglutide is effective for weight management in adults with overweight or obesity without diabetes. The recently published STEP UP trial evaluating semaglutide 7.2 mg provides additional evidence on higher-dose regimens and showed greater weight reduction compared with previously available data, representing a meaningful new contribution to the literature. Longer-term studies are needed to better define the long-term efficacy and safety profile of semaglutide across clinical populations.