Effects of Incretin-based Therapy on High-sensitivity C-reactive Protein in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
- Design
- Meta-analysis · 2851 participants · Biomarker outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: every included trial enrolled adults with type 2 diabetes; study mean ages were between 47.7 and 68.4, and results were reported for subgroups with mean baseline BMI above and below 30.
- Could weight loss explain it?
- PossiblyStudy-level meta-regression found that better glycaemic control and greater BMI decline were associated with larger hs-CRP reductions; this is a between-trial association, not a participant-level mediation analysis, so weight and glycaemic effects are not separated.
- Study tier
- Study tier 2MODERATE: meta-analysis of 28 randomised trials (2,851 participants), but with a biomarker outcome, high heterogeneity (I2 = 88.1%) and many small, partly open-label trials.
- Assessment
- Version 3 · Two reviewers differed; settled by a recorded ruling · 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.
This meta-analysis pooled 28 randomised trials (25 studies, 2,851 adults with type 2 diabetes) comparing incretin-based drugs, either GLP-1 receptor agonists or DPP-4 inhibitors, with placebo or other treatments. Both classes were linked to lower hs-CRP, an inflammation blood marker (all incretin drugs SMD = -0.452; GLP-1 receptor agonists SMD = -0.544), but trials shorter than 24 weeks showed no significant difference. Results varied widely between trials, and larger falls were associated with better blood sugar control and more BMI decline.
01Findings
What the study reported
- Drugs
- Glp-1 receptor agonists, Dpp-4 inhibitors
- Dose
- various
- Route
- various
- Comparator
- placebo or active drugs (controls)
- Treatment duration
- 12 weeks to 104 weeks
- Primary outcome
- Pooled standardised mean difference in serum hs-CRP, incretin-based therapy versus controls
- Effect
- All incretin-based therapies SMD = -0.452 (p < 0.001); GLP-1 RAs SMD = -0.544 (p = 0.003); DPP-4Is SMD = -0.338 (p = 0.026); no significant difference for durations under 24 weeks
- 95% confidence interval
- pooled SMD −0.452, 95% CI −0.688 to −0.217; GLP-1 RAs 95% CI −0.908 to −0.181
- P value
- p < 0.001 (overall); p = 0.003 (GLP-1 RAs)
- Follow-up
- median follow-up of 24 weeks
- Adverse events
- not reported
- Limitations
- The authors note small trials with low power, trials not designed to assess hs-CRP, inconsistent hs-CRP methods and some calculated data; heterogeneity was high, eight parallel and two crossover trials were open-label, and the pooled result combines GLP-1 RAs with DPP-4 inhibitors.
Who was studied
- Mean age
- study means between 47.7 and 68.4 years
- Age min
- 18
- Obesity status
- mixed (subgroups by mean baseline BMI above and below 30)
- Diabetes status
- type 2 diabetes required
- Baseline condition
- type 2 diabetes
- Sample size
- 2851
- Inclusion exclusion
- randomised controlled trials in adults aged more than 18 with T2DM reporting hs-CRP change for intervention and control groups
Study quality details
- Study design
- Meta-analysis
- Sample size
- 2851
- Randomization
- yes
- Blinding
- n/a
- Comparator
- placebo or active drugs (controls)
- Follow up duration
- median follow-up of 24 weeks
- Outcome type
- biomarker
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- 95% CIs reported; high heterogeneity (I2 = 88.1%); Egger test p = 0.103
- Risk of bias
- not assessed
- Funding conflicts
- no
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Nantong University Clinical Medicine Program (2019JQ008)
- Industry funded
- No
- Manufacturer
- not stated in source
- Sponsor role
- not reported
- Author conflicts
- not reported
- Independent replication
- unknown
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.Consistent, but doesn't test the claim
Meta-analysis of 25 RCTs in type 2 diabetes pooling GLP-1 RAs and DPP-4 inhibitors: hs-CRP fell with GLP-1 RAs (SMD = -0.544), with no significant difference under 24 weeks, and across studies more BMI decline was associated with greater hs-CRP reduction (-0.325, 95% CI -0.605 to -0.044). Ecological; it does not separate a weight-independent effect.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Recently, studies had shown that incretin-based therapies could reduce the levels of pro-inflammatory markers. The data on the effects of incretin-based therapies on serum high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetes (T2DM) were inconsistent. [OBJECTIVE] The objective of the study was to assess the effects of incretin-based therapies on hs- CRP in patients with T2DM by meta-analysis. [METHODS] We searched PubMed, EMBASE, the Cochrane Collaboration Library, and Web of Science to identify the eligible randomized clinical trials until August 2019. The pooled standard mean differences (SMD) were calculated by random-effects model using STATA 11.0. [RESULTS] Twenty-five studies with 28 randomized controlled trials were finally included into the meta-analysis. Meta-analysis revealed a significant reduction in hs-CRP following treatment with incretin-based regimens compared to controls (SMD = -0.452, p < 0.001). Subgroup analysis of different class of incretinbased drugs showed that therapy with both dipeptidyl peptidase 4 inhibitors (DPP-4Is, SMD = -0.338, p = 0.026) and glucagonlike peptide 1 receptor agonists (GLP-1 RAs, SMD = -0.544, p = 0.003) caused significant reductions in hs-CRP. Besides, there was a significant reduction in hs-CRP with an intervention duration more than 24 weeks (SMD = -0.465, p = 0.001), while no significant difference with < 24 weeks. Meta-regression analyses showed that better glycemic control and more body mass index (BMI) decline were associated with hs-CRP reduction after incretin-based therapies. [CONCLUSIONS] This meta-analysis suggests that incretin-based therapies, both GLP-1 RAs and DPP-4Is, can cause a significant reduction in hs-CRP in patients with T2DM, which is related to long intervention duration, better glycemic control, and more BMI decline.