Effect of liraglutide on expression of inflammatory genes in type 2 diabetes
- Design
- Randomized trial · 54 participants · Biomarker outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all participants had type 2 diabetes and mean BMI was 30.2; mean age 66.8 falls in the target range, and 13.0% were women.
- Could weight loss explain it?
- UnlikelyNo between-group effect was found, so there is no benefit for weight loss to explain; weight and HbA1c change were not analysed as mediators. Because GLP1R was not detected in the blood cells, the authors suggest any effect of liraglutide on them is most likely indirect.
- Study tier
- Study tier 3LOW: exploratory, unpowered biomarker sub-study of 54 participants from a double-blind randomised placebo-controlled trial, plus in vitro cell work.
- Assessment
- Version 3 · Two independent AI reviews agreed · 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 a sub-study of a 26-week double-blind trial, 54 adults with type 2 diabetes (mean age 66.8) took liraglutide or placebo and had inflammatory gene activity measured in blood immune cells. Within the liraglutide group TNFA fell 26% and IL1B 34%, but these and the other changes did not differ significantly from placebo (p ≥ 0.67 for TNFA and IL1B). The drug's receptor was not detected in the cells, and tests on a cell line showed no direct effect of GLP-1.
01Findings
What the study reported
- Drugs
- Liraglutide
- Dose
- up to 1.8 mg once daily
- Comparator
- placebo (on top of standard of care)
- Treatment duration
- 26 weeks
- Primary outcome
- Change from baseline to end-of-treatment in expression of selected inflammatory genes in peripheral blood mononuclear cells (sub-study; the main trial primary endpoint was arterial FDG uptake)
- Effect
- Within the liraglutide group TNFA expression fell 26% (p = 0.004) and IL1B 34% (p = 0.046) and CCL5 rose (p = 0.002); none differed significantly from placebo (p ≥ 0.67 for TNFA and IL1B; p = 0.36 for CCL5); IFNG and CD163 rose in both groups; GLP1R was undetectable in blood cells
- 95% confidence interval
- 95% CI for within-group change only, e.g. TNFA liraglutide 0.43 (0.15; 0.72); none for between-group differences
- P value
- between groups p ≥ 0.67 (TNFA, IL1B); within liraglutide group TNFA p = 0.004, IL1B p = 0.046
- Follow-up
- 26 weeks
- Adverse events
- not reported
- Limitations
- The sub-study was not the trial's primary aim or powered for it, groups were numerically unbalanced (sex, smoking, SGLT-2 inhibitor use) and sample sizes skewed (31 vs 23); the THP-1 cell model has known limits.
Who was studied
- Mean age
- 66.8 (8.4) years
- Age min
- 50
- Sex distribution
- 7 (13.0%) women
- Bmi mean
- 30.2 (4.9) kg/m2
- Obesity status
- not reported (no BMI entry criterion stated; mean BMI 30.2)
- Diabetes status
- type 2 diabetes required
- Cvd status
- mixed (11 (20.4%) had a history of CVD)
- Ckd status
- not reported (eGFR ≥ 30 required)
- Baseline condition
- type 2 diabetes
- Sample size
- 54
- Inclusion exclusion
- type 2 diabetes, above 50 years, HbA1c ≥ 48 mmol/mol (6.5%), eGFR ≥ 30; no DPP-4 inhibitor or GLP-1 RA in the prior 90 days
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 54
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo (on top of standard of care)
- Follow up duration
- 26 weeks
- Outcome type
- biomarker
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- 95% CIs for within-group change only, none for between-group differences; 31 liraglutide and 23 placebo; sub-study not powered (power calculated for the main trial)
- Risk of bias
- not assessed
- Funding conflicts
- partial
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk A/S and Skibsreder Per Henriksen, R. og hustrus fund; internal funding from Steno Diabetes Center Copenhagen and Rigshospitalet
- Industry funded
- Partial
- Manufacturer
- Novo Nordisk A/S
- Sponsor role
- not reported
- Author conflicts
- Four authors had Novo Nordisk shares, two are now Novo Nordisk employees, and others received consultancy fees or grants from Novo Nordisk and other companies; two declare none.
- 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.
03Claims
Claims this study bears on
- GLP-1 receptor agonist treatment reduces systemic inflammatory markers beyond what can be explained by treatment-associated weight loss.Mechanism only
Out of scope for O3 (IN-039, owner-decided 2026-09-18): the record reports TNFA messenger RNA in peripheral blood mononuclear cells on the delta-delta-Ct scale, not circulating TNF-alpha protein, and the between-group comparison is null (p = 0.67). It is also a 54-of-102 sub-study of NCT03449654, so under the one-entry-per-trial rule it is a companion analysis carrying no independent weight. Kept as trial-locating; no RoB 2.
04Source
The source, as retrieved
Abstract
Anti-inflammatory effects of glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment in T2D may contribute to the cardiovascular benefits observed with GLP-1 RAs in outcome studies. We investigated if the GLP-1 RA liraglutide exerts anti-inflammatory effects through modulation of inflammatory gene expression in peripheral blood mononuclear cells (PBMCs). From 54 participants of a double-blinded trial where individuals with type 2 diabetes (T2D) were randomized to liraglutide (1.8 mg/day) or placebo for 26 weeks, a sub-study was performed in which PBMCs were extracted from fresh blood at study start and at end-of-treatment. The expression of selected inflammatory genes in PBMCs were measured by quantitative real-time polymerase chain reaction (PCR). Moreover, the expression of the GLP-1 receptor (GLP1R) was examined in a subset (n = 40) of the PBMC samples. The human monocytic cell line THP-1 was used for in vitro GLP-1 exposure experiments. The expression of tumor necrosis factor-α (TNFA) (p = 0.004) and interleukin-1β (IL1B) was downregulated (p = 0.046) in the liraglutide-treated group (n = 31), and unchanged in the placebo group (n = 21, p ≥ 0.11), with no significant differences between the two groups (p ≥ 0.67). The expression of interferon-γ (IFNG) and cluster of differentiation 163 (CD163) were upregulated in both groups (p ≤ 0.006) with no differences between groups (p ≥ 0.47). C-C Motif Chemokine Ligand 5 (CCL5) was upregulated in the liraglutide-treated group (p = 0.002) and unchanged in the placebo group (p = 0.14), with no significant difference between groups (p = 0.36). Intercellular adhesion molecule 1 (ICAM1) was unchanged in both groups (p ≥ 0.43). GLP1R expression in the PBMCs was undetectable. In vitro experiments showed no effect of GLP-1 treatment on inflammatory gene expression in THP-1 cells. GLP1R expression in THP-1 cells was not detectable. In summary, we observed a discrete modulatory effect of liraglutide on the expression of inflammatory genes in PBMCs. The lack of evidence for GLP1R expression in PBMCs and THP-1 cells suggests that possible effects of liraglutide on the PBMCs' gene expression are most likely indirect. Further investigations are needed to establish the anti-inflammatory potential of GLP-1 RAs.