Effect of liraglutide on expression of inflammatory genes in type 2 diabetes.

Zobel EH, Ripa RS, von Scholten BJ, Rotbain Curovic V, Kjaer A, Hansen TW, Rossing P, Størling J

Scientific reports17 Sept 2021Cited by 51 (Europe PMC)

PMID34535716PMCIDPMC8448739DOI10.1038/s41598-021-97967-0PepBankPUB-34535716

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

9 results from studies that gave the peptide. 9 results from people.

01HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, TNFA expression in blood mononuclear cells did not differ significantly between liraglutide and placebo.
In plain wordsIn adults with type 2 diabetes, TNF-alpha gene activity in blood immune cells was not clearly different with liraglutide than with placebo.
Peptide
Liraglutide
Outcome
No significant changeTNFA expression in PBMCs, liraglutide versus placebo
Study
n = 52
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571603
02HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, IL1B expression in blood mononuclear cells did not differ significantly between liraglutide and placebo.
In plain wordsIn adults with type 2 diabetes, IL-1 beta gene activity in blood immune cells was not clearly different with liraglutide than with placebo.
Peptide
Liraglutide
Outcome
No significant changeIL1B expression in PBMCs, liraglutide versus placebo
Study
n = 52
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571604
03HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, TNFA expression in blood mononuclear cells fell significantly from baseline in the liraglutide group.
In plain wordsIn adults with type 2 diabetes, liraglutide was followed by lower TNF-alpha gene activity in blood immune cells compared with baseline.
Peptide
Liraglutide
Outcome
DecreaseTNFA expression in PBMCs, within liraglutide group
Study
n = 31
Comparator
Baseline
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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)
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571601
04HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, IL1B expression in blood mononuclear cells fell significantly from baseline in the liraglutide group.
In plain wordsIn adults with type 2 diabetes, liraglutide was followed by lower IL-1 beta gene activity in blood immune cells compared with baseline.
Peptide
Liraglutide
Outcome
DecreaseIL1B expression in PBMCs, within liraglutide group
Study
n = 31
Comparator
Baseline
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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)
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571602
05HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, CCL5 expression in blood mononuclear cells rose significantly from baseline in the liraglutide group.
In plain wordsIn adults with type 2 diabetes, liraglutide was followed by higher CCL5 gene activity in blood immune cells compared with baseline.
Peptide
Liraglutide
Outcome
IncreaseCCL5 expression in PBMCs, within liraglutide group
Study
n = 31
Comparator
Baseline
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571607
06HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, IFNG expression rose in both groups with no significant difference between liraglutide and placebo.
In plain wordsIn adults with type 2 diabetes, interferon-gamma gene activity rose in both groups, with no clear difference between liraglutide and placebo.
Peptide
Liraglutide
Outcome
No significant changeIFNG expression in PBMCs, liraglutide versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571605
07HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, CD163 expression rose in both groups with no significant difference between liraglutide and placebo.
In plain wordsIn adults with type 2 diabetes, CD163 gene activity rose in both groups, with no clear difference between liraglutide and placebo.
Peptide
Liraglutide
Outcome
No significant changeCD163 expression in PBMCs, liraglutide versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571606
08HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, CCL5 expression in blood mononuclear cells did not differ significantly between liraglutide and placebo.
In plain wordsIn adults with type 2 diabetes, CCL5 gene activity in blood immune cells was not clearly different with liraglutide than with placebo.
Peptide
Liraglutide
Outcome
No significant changeCCL5 expression in PBMCs, liraglutide versus placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571608
09HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, ICAM1 expression in blood mononuclear cells was unchanged in both the liraglutide and placebo groups.
In plain wordsIn adults with type 2 diabetes, ICAM1 gene activity in blood immune cells did not change in either the liraglutide or placebo group.
Peptide
Liraglutide
Outcome
No significant changeICAM1 expression in PBMCs
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg/day · 26 weeksAs given in this study (human).
Source sentences
Summary
Intercellular adhesion molecule 1 (ICAM1) was unchanged in both groups (p ≥ 0.43).
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3453571609

Studies that did not test the peptide alone3

In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Liraglutide.

10HumanNot a test of Liraglutide aloneRandomized controlled trialMechanism
In blood mononuclear cells from adults with type 2 diabetes, GLP-1 receptor expression was undetectable.
In plain wordsIn blood immune cells from adults with type 2 diabetes, the GLP-1 receptor could not be detected.
Peptide
Liraglutide
Outcome
Not applicableGLP-1 receptor expression in PBMCs
Study
n = 40
Outcome group
Receptor activity and mechanism · Immune and inflammation
Source sentences
Summary
Moreover, the expression of the GLP-1 receptor (GLP1R) was examined in a subset (n = 40) of the PBMC samples.
2 context sentences(design, population, supporting numbers)
Summary · context
GLP1R expression in the PBMCs was undetectable.
Summary · context
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.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3453571610
11LabNot a test of Liraglutide aloneIn vitro (cells)Mechanism
In human THP-1 monocytic cells, GLP-1 exposure had no effect on inflammatory gene expression.
In plain wordsIn lab tests on human immune-type cells, GLP-1 did not change inflammatory gene activity.
Peptide
Liraglutide
Outcome
No significant changeInflammatory gene expression after GLP-1 exposure in THP-1 cells
Study
humann: not reported in source
THP-1 monocytic cell line
Outcome group
Inflammation markers · Immune and inflammation
Source sentences
Summary
The human monocytic cell line THP-1 was used for in vitro GLP-1 exposure experiments.
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro experiments showed no effect of GLP-1 treatment on inflammatory gene expression in THP-1 cells.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3453571611
12LabNot a test of Liraglutide aloneIn vitro (cells)Mechanism
In human THP-1 monocytic cells, GLP-1 receptor expression was not detectable.
In plain wordsIn lab tests on human immune-type cells, the GLP-1 receptor could not be detected.
Peptide
Liraglutide
Outcome
Not applicableGLP-1 receptor expression in THP-1 cells
Study
humann: not reported in source
THP-1 monocytic cell line
Outcome group
Receptor activity and mechanism · Immune and inflammation
Source sentences
Summary
The human monocytic cell line THP-1 was used for in vitro GLP-1 exposure experiments.
1 context sentence(design, population, supporting numbers)
Summary · context
GLP1R expression in THP-1 cells was not detectable.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-3453571612

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 11:11 UTC
Study results updated
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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