Anti-inflammatory effect of semaglutide: updated systematic review and meta-analysis
- Design
- Meta-analysis · 26131 participants · Biomarker outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with type 2 diabetes.
- 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 13 randomized trials, semaglutide lowered CRP (a blood marker of inflammation) versus placebo or other drugs, with very high heterogeneity (I2 82-92%). The drop was larger in people without type 2 diabetes than in people with it (interaction p ≤ 0.0001). The analysis did not test cardiovascular events.
What the study reported
- Drugs
- Semaglutide
- Route
- subcutaneous and oral
- Comparator
- placebo or other glucose-lowering drugs
- 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
- mixed: type 2 diabetes and/or overweight or obesity (5 trials in T2D, 6 in overweight or obesity without T2D)
- Diabetes status
- mixed (with and without type 2 diabetes)
- Sample size
- 26131
Study quality details
- Study design
- Meta-analysis
- Sample size
- 26131
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo or other glucose-lowering drugs
- 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 -0
- 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.
Low confidence in the review · AMSTAR 2 · AI: two passes agreed (item splits settled by owner ruling)
Why: one critical item fails: list of excluded studies, with reasons.
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 | Partial Yes |
| 5 Study selection done by two reviewers independently | No |
| 6 Data extraction done by two reviewers independently | No |
| 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 | Yes |
| 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 | Yes |
| 16 Review authors' conflicts of interest and funding reported | Yes |
Where the two reviewers differed: item 5 (study selection done by two reviewers independently): one read No, the other Yes; settled at No by a recorded ruling; item 6 (data extraction done by two reviewers independently): one read No, the other Yes; 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
- Journal submission funded by Novo Nordisk Pharma Argentina S.A., which the authors say did not influence the content or take part in the study (full text)
- Industry funded
- Yes
- Manufacturer
- Novo Nordisk
- Sponsor role
- not reported in abstract
- Author conflicts
- WM, ML and DS have served as a speaker from Novo Nordisk. The remaining 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
- 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] The anti-inflammatory effect could be one of the mechanisms by which semaglutide reduces cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) and/or obesity. Determining the anti-inflammatory effect of semaglutide was the objective of this systematic review and meta-analysis. [METHODS] This meta-analysis was performed according to the PRISMA guidelines. A literature search was performed to detect randomised clinical trials that have quantified the effect of semaglutide on C-reactive protein (CRP) levels compared to placebo or a control group (other glucose-lowering drugs). The primary outcome was CRP index (final CRP/basal CRP). A random-effects model was used. [RESULTS] Thirteen randomised clinical trials were considered eligible (n = 26,131). Overall, semaglutide therapy was associated with lower CRP index values compared to the placebo group (SMD -0.56; 95% CI -0.69 to -0.43, I 2 92%) or the control group (SMD -0.45; 95% CI -0.68 to -0.23, I 2 82%).Such an association was similarly observed when different treatment regimens (subcutaneous vs. oral) or different populations (patients with or without T2DM) were analysed. The sensitivity analysis showed that the results were robust. [CONCLUSION] The present meta-analysis demonstrated that the use of semaglutide was associated with a reduction in inflammation irrespective of the population evaluated or the treatment regimen used. These findings would explain one of the mechanisms by which semaglutide reduces cardiovascular events. [SYSTEMATIC REVIEW REGISTRATION] PROSPERO [CRD42024500551].