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Cited by 59Diabetes Treatment and ManagementAdipokines, Inflammation, and Metabolic DiseasesDiabetes Management and Research

The effect of GLP ‐1 receptor agonists on circulating inflammatory markers in type 2 diabetes patients: A systematic review and meta‐analysis

Open access
Ren, Yifan, Chen, Yuzhang, Zheng, Wenbin, Kong, Wen, Liao, Yunfei, Zhang, Jiaoyue, Wang, Meng, Zeng, Tianshu·2025·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.16366
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Abstract

AIM: To investigate whether the antidiabetic agent glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can exert anti-inflammatory effects while lowering blood glucose, we performed a meta-analysis and systematic review. METHODS: We searched 4 online databases (Medline, Embase, Cochrane Library and the Web of Science) for randomised controlled trials (RCTs) that examined changes after GLP-1RAs intervention in commonly accepted biomarkers of inflammation: C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1(MCP-1) and advanced glycation end products (AGEs). RESULTS: , glycated haemoglobin (HbA1c) 8.28% and diabetes duration 7.27 years. GLP-1 RAs treatment, compared to placebo or conventional diabetes therapies (including oral medicine and insulin), resulted in significant reductions in CRP, TNF-α, IL-6, IL-1β and leptin (standard mean difference [SMD] -0.63 [-1.03, -0.23]; SMD -0.92 [-1.57, -0.27]; SMD -0.76 [-1.32, -0.20], SMD -3.89 [-6.56, -1.22], SMD -0.67 [-1.09, -0.26], respectively), as well as significant increases in adiponectin (SMD 0.69 [0.19, 1.19]). CONCLUSIONS: Our meta-analysis demonstrates that GLP-1 RAs exert significant anti-inflammatory effects in patients with T2DM. Our findings provide important insights that may guide the therapeutic application of GLP-1 RAs and inform the development of related therapies.

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Crossref · 10.1111/dom.16366

Cites

135 of 136 references verified0 citation errors · 1 not checkable

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Claims the paper makes

17 of 40 cited sources checked · 8 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The anti-inflammatory effects of GLP-1 RAs and SGLT2i are not fully elucidated.

    “This gap in knowledge is especially pronounced in the case of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i), which have shown promise in reducing cardiovascular and renal risks but whose anti-inflammatory effects are not fully elucidated.23”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [23] 23. Das SR et al. 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution set Oversight Committee. J Am Coll Cardiol. 2020;76:1117-1145. doi:10.1016/j.jacc.2020.05.037 source

      The Introduction says the mechanisms behind cardiovascular and renal benefits remain uncertain, and the GLP-1RA Mechanisms of Action section identifies anti-inflammatory effects. The SGLT2 Inhibitors Mechanism of Action section also says its mechanisms of benefit are not fully elucidated. However, the paper does not specifically say that the anti-inflammatory effects of both drug classes are not fully elucidated; it does not identify anti-inflammatory effects for SGLT2 inhibitors. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Findingown data

    After excluding the study of Forst et al., the pooled effect of three studies shows a statistical decline in MCP-1 level.

    “after excluding the study of Forst et al., 79 the pooled effect of three studies 72,82 shows a statistical decline in MCP-1 level”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Forst et al., 79

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [72] 72. Gurkan E, Tarkun I, Sahin T, Cetinarslan B, Canturk Z. Evaluation of exenatide versus insulin glargine for the impact on endothelial func- tions and cardiovascular risk markers. Diabetes Res Clin Pract. 2014; 106:567-575. doi:10.1016/j.diabres.2014.09.046 source
    • cites [82] 82. Bunck MC, Diamant M, Eliasson B, et al. Exenatide affects circulat- ing cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care. 2010;33:1734-1737. doi:10.2337/ dc09-2361 source
  • Premisecitation

    The cardiovascular benefits of GLP-1 receptor agonists cannot be explained merely by improved blood glucose control and weight loss.

    “These benefits cannot be explained merely by improved blood glucose control and weight loss.97”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [97] 97. Rizzo M, Nikolic D, Patti AM, et al. GLP-1 receptor agonists and reduction of cardiometabolic risk: potential underlying mechanisms. Biochim Biophys Acta Mol Basis Dis. 2018;1864:2814-2821. doi:10. 1016/j.bbadis.2018.05.012 source
  • Premisecitation

    Clinical research supports the validity of the anti-inflammatory properties of GLP-1 receptor agonists in the therapeutic setting.

    “Clinical research also supports the validity of these antiinflammatory properties in the therapeutic setting.107”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [107] 107. Qaseem A, Obley AJ, Shamliyan T, et al. Newer pharmacologic treat- ments in adults with type 2 diabetes: a clinical guideline from the American College of Physicians. Ann Intern Med. 2024;177:658-666. doi:10.7326/m23-2788 114. source

      The Methods and Recommendations (Recommendation 1; page unavailable) discuss clinical outcomes of GLP-1 agonist treatment, including mortality, cardiovascular events, stroke, and weight loss. They do not address whether those benefits reflect anti-inflammatory properties. Searches for inflammation and anti-inflammatory effects found no passage supporting the attributed claim. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Premisecitation

    In the SELECT trial, a 20% reduction in cardiovascular risk has been observed in obese individuals without diabetes treated with semaglutide.

    “In the SELECT trial, 98 a 20% reduction in cardiovascular risk has been observed in obese individuals without diabetes treated with semaglutide.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [98] 98. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221-2232. doi:10.1056/NEJMoa2307563 source

      The Discussion reports a 20% reduction in the composite risk of cardiovascular death, nonfatal heart attack, or nonfatal stroke with semaglutide. The claim omits that SELECT enrolled participants with preexisting cardiovascular disease and either overweight or obesity, not obese individuals without diabetes generally. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 13
  • May combine two claims. 27
  • The quote only partly states this claim. 2

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Risk of bias was assessed using the Cochrane Risk-of-Bias 2 (RoB 2) tool.

    “The assessment of potential biases in randomised trials was conducted using the Cochrane Risk-of-Bias 2 (RoB 2) tool.85”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [85] 85. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for asses- sing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi:10. 1136/bmj.l4898 source

  • May combine two claims.

    Premisecitation

    Animal experiments have shown that TNF-α-blocking Infliximab improves renal function through attenuating fibrosis and decreasing albumin excretion in a diabetic nephropathy rat model.

    “Furthermore, animal experiments have shown that TNF-α-blocking Infliximab improves renal function through attenuating fibrosis 20 and decreasing albumin excretion in a diabetic nephropathy rat model, 21,22”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [20] 20. Nageeb MM, Talaat A, Reda SM, Elsammak GA. Infliximab abrogates adenine-induced chronic kidney disease via modulation of the MAPK/JNK/ASK signaling pathway in rats. Naunyn Schmiedebergs Arch Pharmacol. 2024;397:207-219. doi:10.1007/s00210-023- 02585-4 source
    • cites [21] 21. Chen J, Liu Q, He J, Li Y. Immune responses in diabetic nephropathy: pathogenic mechanisms and therapeutic target. Front Immunol. 2022;13:958790. doi:10.3389/fimmu.2022.958790 source

      The TNF-α subsection under “Inhibition of soluble pro-inflammatory mediators” reports that infliximab reduced TNF-α expression and improved diabetic nephropathy symptoms in diabetic mice. It does not report an infliximab experiment in rats or attribute reduced fibrosis or albumin excretion to infliximab. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [22] 22. Moriwaki Y, Inokuchi T, Yamamoto A, et al. Effect of TNF-alpha inhi- bition on urinary albumin excretion in experimental diabetic rats. Acta Diabetol. 2007;44:215-218. doi:10.1007/s00592-007-0007-6 source

  • May combine two claims.

    Premisecitation

    Prior meta-analysis supported anti-inflammatory effects of GLP-1 RAs but was limited by number of studies and range of biomarkers evaluated.

    “While prior meta-analysis 31 have supported these effects, they were limited by the number of studies and range of biomarkers evaluated.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [31] 31. Bray JJH, Foster-Davies H, Salem A, et al. Glucagon-like peptide-1 receptor agonists improve biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis of randomised con- trolled trials. Diabetes Obes Metab. 2021;23(8):1806-1822. doi:10. 1111/dom.14399 source

      The Abstract reports anti-inflammatory effects from 40 eligible RCTs. Sections 3.2 and 2.3 show that fewer trials reported some biomarkers and that two biomarkers were excluded for insufficient data. This supports limits in biomarker-specific evidence, but the paper does not characterize its overall 40-trial analysis as limited by the number of studies or the range of biomarkers evaluated. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Anti-inflammatory drugs such as Canakinumab, an IL-1β monoclonal antibody, have effectiveness independent from lipid-lowering on reducing cardiovascular events in patients with coronary artery disease.

    “Anti-inflammatory drugs such as Canakinumab, an IL-1β monoclonal antibody, have been demonstrated to have effectiveness independent from lipid-lowering on reducing cardiovascular events in patients with coronary artery disease.7,8”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [7] 7. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1beta inhibi- tion and the prevention of recurrent cardiovascular events: rationale and design of the canakinumab anti-inflammatory thrombosis out- comes study (CANTOS). Am Heart J. 2011;162:597-605. doi:10. 1016/j.ahj.2011.06.012 source
    • cites [8] 8. Li B, Li W, Li X, Zhou H. Inflammation: a novel therapeutic target/dir- ection in atherosclerosis. Curr Pharm des. 2017;23:1216-1227. doi: 10.2174/1381612822666161230142931 source

      The IL-1 section (page unavailable) identifies canakinumab as an IL-1β-neutralizing monoclonal antibody and says IL-1β inhibition does not adversely affect lipid levels. But it describes the cardiovascular-outcomes trial as ongoing; it does not report a demonstrated reduction in cardiovascular events, independent of lipid lowering or otherwise. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Accumulating evidence suggests that a subclinical inflammatory reaction participates in the pathogenesis of T2DM and its cardiorenal complications, with elevated plasma levels of pro-inflammatory cytokines.

    “Accumulating evidence suggests that a subclinical inflammatory reaction participates in the pathogenesis of T2DM and its cardiorenal complications, with elevated plasma levels of pro-inflammatory cytokines, including tumour necrosis factor-alpha (TNF-α), 11 interleukin-1 beta (IL-1β), 12 IL-6 13,14 and other IL-1-dependent pro-inflammatory cytokines and chemokines.[15][16][17][18]”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [11] 11. Akash MSH, Rehman K, Liaqat A. Tumor necrosis factor-alpha: role in development of insulin resistance and pathogenesis of type 2 dia- betes mellitus. J Cell Biochem. 2018;119:105-110. doi:10.1002/jcb. 26174 source
    • cites [12] 12. Spranger J, Kroke A, Möhlig M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes. Diabetes. 2003;52(3):812-817. doi:10.2337/diabetes.52.3.812 source

      The Abstract reports that a subclinical inflammatory reaction may contribute to type 2 diabetes and links circulating IL-6 and IL-1β patterns to future diabetes risk. The paper does not address cardiorenal complications or establish that all the listed cytokines are individually elevated: its Results report no significant difference in IL-1β levels between cases and controls. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [13] 13. Feve B, Bastard JP. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol. 2009;5:305-311. doi: 10.1038/nrendo.2009.62 source
    • cites [14] 14. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes melli- tus. Jama. 2001;286:327-334. doi:10.1001/jama.286.3.327 source

  • May combine two claims.

    Premisecitation

    High-quality meta-analyses have shown that GLP-1 RAs can decrease the risk of major adverse cardiovascular events (MACE) and deterioration of renal function in individuals with T2DM.

    “High-quality meta-analyses have shown that GLP-1 RAs, regardless of whether they have an exendin-4-based structure or not, can decrease the risk of major adverse cardiovascular events (MACE) and deterioration of renal function in individuals with T2DM, 24 demonstrating comparable clinical effects to SGLT2i.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] 24. Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of random- ised trials. Lancet Diabetes Endocrinol. 2021;9:653-662. doi:10. 1016/S2213-8587(21)00203-5 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DPP4 inhibitors exhibit cardiovascular neutrality in T2DM patients.

    “have shown that DPP4i exhibit cardiovascular neutrality in T2DM patients.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [134] source
    • cites [135] source
    • cites [136] source

      The Discussion (p. 8) reports no change in major adverse cardiovascular events with sitagliptin and says trials of two other DPP-4 inhibitors likewise found no increase or decrease in those events. But it also reports increased heart-failure hospitalization with saxagliptin, so unqualified cardiovascular neutrality for the class overstates the evidence. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    GLP-1 receptor agonists exert heart and renal protective effects in T2DM patients, mainly manifesting in reducing the risk of individual MACE components, all-cause mortality, hospital admission for heart failure and worsening kidney function.

    “the GLP-1 RAs have been proven to exert heart and renal protective effects in T2DM patients, mainly manifesting in reducing the risk of individual MACE components, all-cause mortality, hospital admission for heart failure and worsening kidney function.24,[93][94][95]”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [24] 24. Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of random- ised trials. Lancet Diabetes Endocrinol. 2021;9:653-662. doi:10. 1016/S2213-8587(21)00203-5 source
    • cites [93][94][95]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Albiglutide demonstrated a 22% reduction in the risk of major cardiovascular events compared to placebo in T2DM patients with cardiovascular disease in the HARMONY outcomes trial, without significant weight loss.

    “Albiglutide also demonstrated a 22% reduction in the risk of major cardiovascular events compared to placebo in T2DM patients in comorbidity with cardiovascular disease in the HARMONY outcomes trial, 99 without significant weight loss.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [99] 99. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and car- diovascular outcomes in patients with type 2 diabetes and cardio- vascular disease (Harmony outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392:1519-1529. doi:10.1016/ s0140-6736(18)32261-x 100. Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and Management of Obesity. N Engl J Med. 2017;376:254-266. doi:10. 1056/NEJMra1514009 101. source

  • May combine two claims.

    Premisecitation

    DPP4 inhibitors, by blocking DPP-4, raise the amounts of intact GLP-1 but reduce the level of GLP-1 (9-36) and increase other peptides degraded by DPP-4, many of which directly affect the heart and vasculature.

    “DPP4i, by blocking DPP-4, raise the amounts of intact GLP-1 but reduce the level of GLP-1 (9-36) and increase other peptides degraded by DPP-4, many of which directly affect the heart and vasculature.138,139”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [138] source
    • cites [139] source

  • May combine two claims.

    Premisecitation

    The evidence supporting the cardiovascular benefits of GLP-1 receptor agonists is more compelling, likely because of the higher pharmacological GLP-1 levels achieved by GLP-1 receptor agonists compared to the physiological levels with DPP-4 inhibitors.

    “the evidence supporting the cardiovascular benefits of GLP-1RAs is more compelling, 95 likely because of the higher pharmacological GLP-1 levels achieved by GLP-1RAs compared to the physiological levels with DPP-4 inhibitors.127”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [95] 95. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and car- diovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375: 311-322. doi:10.1056/NEJMoa1603827 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [127] source

  • May combine two claims.

    Findingown data

    The meta-analysis included 52 eligible RCTs with 4734 participants.

    “This meta-analysis included 52 eligible RCTs (n = 4734) with a median follow-up of 24 weeks, a mean age of 54.13 years, 44.46% females, body mass index (BMI) 29.80 kg/m 2 , glycated haemoglobin (HbA1c) 8.28% and diabetes duration 7.27 years.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After trim and fill, five potential missing studies for CRP were identified, suggesting potential publication bias.

    “After applying the 'trim and fill' method, five potential missing studies for CRP, nine for TNF-α and five for IL-6 were identified in the funnel plot, suggesting the presence of potential publication bias.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In primary subgroup analysis, the GLP-1 RA plus oral antidiabetic drug versus oral antidiabetic drug subgroup contributed most to the effect estimate for adiponectin (SMD 2.25, 95% CI 0.86 to 3.64, I2 84%, p < 0.01).

    “adiponectin (SMD = 2.25 [0.86, 3.64], I 2 = 84%, p < 0.01)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After trim and fill, five potential missing studies for IL-6 were identified, suggesting potential publication bias.

    “After applying the 'trim and fill' method, five potential missing studies for CRP, nine for TNF-α and five for IL-6 were identified in the funnel plot, suggesting the presence of potential publication bias.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There is no significant difference among different types of GLP-1 receptor agonists (exenatide, liraglutide and dulaglutide) in reducing inflammation, with almost all subgroup difference tests yielding p-values > 0.05.

    “The results revealed that there is no significant difference among different types of GLP-1RAs (exenatide, liraglutide and dulaglutide), with almost all tests for subgroup differences yielding p-values >0.05”
    • Also stated in: § Additional information · plain
      “The molecular types of GLP-1 RAs have a negligible impact on their anti-inflammatory effects.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In primary subgroup analysis, the GLP-1 RA plus oral antidiabetic drug versus oral antidiabetic drug subgroup contributed most to the effect estimate for IL-6 (SMD -1.31, 95% CI -2.57 to -0.04, I2 88%, p = 0.04).

    “IL-SMD = À1.31[À2.57,À0.04],I 2 = 88%, p = 0.04”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After trim and fill, nine potential missing studies for TNF-α were identified, suggesting potential publication bias.

    “After applying the 'trim and fill' method, five potential missing studies for CRP, nine for TNF-α and five for IL-6 were identified in the funnel plot, suggesting the presence of potential publication bias.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Publication bias was assessed through funnel plots and Egger's test.

    “Potential publication bias was assessed through funnel plots and Egger's test (significance threshold: α = 0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    26 of 52 included studies were classified as low risk of bias, and 26 as some concerns.

    “26 of the 52 studies were classified as having a 'low risk of bias', while the remaining 26 studies were classified as having 'some concerns' regarding overall bias.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    If funnel plot asymmetry was detected, the trim-and-fill method was applied to adjust for potential effects of unpublished studies.

    “If funnel plot asymmetry was detected, we applied the trim-and-fill method to adjust for the potential effects of unpublished studies.90”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90] 90. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-anal- ysis detected by a simple, graphical test. BMJ. 1997;315:629-634. doi:10.1136/bmj.315.7109.629 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The protocol was registered in PROSPERO before commencing the literature search.

    “The meta-analysis followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, and the protocol was registered in PROSPERO (registration number CRD42023476506) before commencing the literature search.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites CRD42023476506

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Conventional CRP and hs-CRP were pooled in the same analysis because both assess identical inflammatory outcomes.

    “Additionally, studies using conventional CRP and hs-CRP were pooled in the same analysis, as both assess identical inflammatory outcomes.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    For multi-arm trials with a common intervention group, the common group was divided equally into multiple smaller samples to avoid inflating the sample size.

    “For multi-arm trials with a common intervention group reported in the same article, 51,55,71,77 the common group was divided equally into multiple smaller samples to avoid inflating the sample size improperly, and then all the pairwise comparison combinations were included in the meta-analysis following the Cochrane Handbook.86”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] 86. Higgins JPT, Gren S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collabo- ration, Available from handbook.cochrane.org. [updated March 2011] 2011.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Sensitivity analysis sequentially excluded each study and re-ran the meta-analysis to assess robustness.

    “In sensitivity analysis, we sequentially excluded each study and re-ran the meta-analysis to assess the robustness of the results and identify any studies that might have had a disproportionate influence on the overall findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The meta-analysis followed PRISMA guidelines.

    “The meta-analysis followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, and the protocol was registered in PROSPERO (registration number CRD42023476506) before commencing the literature search.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Our study strictly focused on individuals with type 2 diabetes and excluded those with prediabetes, thereby enhancing specificity and relevance of findings.

    “Additionally, our study strictly focused on individuals with type 2 diabetes and excluded those with prediabetes, thereby enhancing the specificity and relevance of our findings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The quality and participants of the included studies varied, which might affect the reliability of the pooled estimates.

    “The quality and participants of the included studies varied, which might affect the reliability of the pooled estimates.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    GLP-1 receptor agonists demonstrate superior anti-inflammatory effects compared to metformin but do not show a significant advantage over DPP-4 inhibitors.

    “GLP-1 RAs demonstrate superior antiinflammatory effects compared to metformin but do not show a significant advantage over DPP-4i.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Although Egger's test did not indicate significant publication bias for CRP, trim and fill identified asymmetry in the funnel plot, suggesting potential bias.

    “Although Egger's test did not indicate significant publication bias for CRP (p = 0.2158), the trim and fill method still identified asymmetry in the funnel plot, suggesting potential bias.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Via visual inspection of the funnel plot and Egger's test, publication bias for IL-6 and TNF-alpha appeared, suggesting that small sample studies were more likely to report significant anti-inflammatory benefits of GLP-1 receptor agonists.

    “Via visual inspection of the funnel plot and Egger's test, publication bias for IL-6 and TNF-α appeared, suggesting that small sample studies were more likely to report significant anti-inflammatory benefits of GLP-1RAs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    After adjusting for publication bias using the trim and fill method, the funnel plot still showed negative SMD values for CRP and IL-6, suggesting that the findings are relatively reliable.

    “After adjusting for publication bias using the trim and fill method, the funnel plot still showed negative SMD values for CRP and IL-6, suggesting that our findings are relatively reliable.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    The bias assessment classified all studies as either 'low risk' or 'some concerns', with the 'some concerns' rating owing primarily to differences in administration routes (e.g. subcutaneous vs. oral) that impede blinding.

    “despite the bias assessment classifying all studies as either 'low risk' or 'some concerns', with the 'some concerns' rating owing primarily to differences in administration routes (e.g.subcutaneous vs. oral) that impede blinding.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The secondary subgroup analysis based on the type of GLP-1 receptor agonists and oral hypoglycemic agents conducted within pre-existing subgroups includes a limited number of studies, the majority of which have small sample sizes; therefore, the results should be interpreted with caution.

    “the secondary subgroup analysis based on the type of GLP-1RAs and oral hypoglycemic agents conducted within pre-existing subgroups includes a limited number of studies, the majority of which have small sample sizes; therefore, the results should be interpreted with caution.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Sensitivity analysis for CRP, TNF-α, IL-6, IL-1β, leptin and adiponectin demonstrated that neither pooled effect size nor statistical significance changed significantly, illustrating results for these biomarkers are relatively reliable.

    “Fortunately, sensitivity analysis for CRP, TNF-α, IL-6, IL-1β, leptin and adiponectin demonstrated that neither the pooled effect size nor the statistical significance changed significantly, illustrating that our meta-analysis results of these inflammation biomarkers are relatively reliable (Supplementary Figure 3).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The research was limited to circulating inflammatory markers, which may not adequately represent the intricate inflammatory mechanisms in T2DM.

    “the research we conducted was limited to circulating inflammatory markers, which may not adequately represent the intricate inflammatory mechanisms in T2DM.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    GLP-1 receptor agonists have shown a significant reduction in HbA1C and weight, with minimal risk of hypoglycemia.

    “The GLP-1 RAs have shown a significant reduction in HbA1C and weight, with minimal risk of hypoglycemia.92”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] 92. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2015;6:19- 28. doi:10.1177/2042018814559725 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    CKD progression is significantly influenced by residual inflammatory risk.

    “Similarly, chronic kidney disease (CKD) progression is also significantly influenced by residual inflammatory risk.9”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] 9. Ridker PM, Tuttle KR, Perkovic V, Libby P, MacFadyen JG. Inflamma- tion drives residual risk in chronic kidney disease: a CANTOS sub- study. Eur Heart J. 2022;43:4832-4844. doi:10.1093/eurheartj/ ehac444 source

  • May combine two claims.

    Premisecitation

    Native GLP-1 regulates cardiovascular function via the GLP-1 receptor or through GLP-1 (9-36), a metabolite formed by DPP-4 cleavage.

    “native GLP-1 regulates cardiovascular function via the GLP-1 receptor or through GLP-1 (9-36), a metabolite formed by DPP-4 cleavage.137”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [137] source

  • May combine two claims.

    Premisereasoning

    Since GLP-1 receptor agonists are not degraded by DPP-4, they act predominantly via the GLP-1 receptor instead of GLP-1 (9-36).

    “Since GLP-1RAs are not degraded by DPP-4, they act predominantly via the GLP-1 receptor instead of GLP-1 (9-36).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    GLP-1 receptor agonists have an overall impact on inflammatory biomarkers and inhibit the inflammatory process.

    “We therefore tend to support that GLP-1 RAs have an overall impact on inflammatory biomarkers and inhibit the inflammatory process.”
    Quote in the paperSubstantial claim
41 of 41

  • The paper relies on this without support.

    The circulating biomarkers selected (CRP, TNF-α, IL-6, IL-1β, leptin, adiponectin, PAI-1, MCP-1 and AGEs) are valid indicators of anti-inflammatory effects in T2DM.

    “commonly accepted biomarkers of inflammation: C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1(MCP-1) and advanced glycation end products (AGEs).”

  • The paper relies on this without support.

    Circulating inflammatory marker levels adequately reflect the inflammatory process relevant to T2DM and cardiovascular risk.

    “the research we conducted was limited to circulating inflammatory markers, which may not adequately represent the intricate inflammatory mechanisms in T2DM.”

  • The paper relies on this without support.

    Reducing circulating inflammatory markers translates into clinical cardiovascular benefit in T2DM patients.

    “The anti-inflammatory effects of GLP-1RAs support their use in T2DM patients with elevated inflammation or high cardiovascular risk, per current guidelines.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • An included T2DM study is cited as an impaired-glucose-tolerance trial

    Major

    Table 1 classifies study 33 as involving T2DM patients, whereas its cited title describes patients with impaired glucose tolerance. This conflicts with the stated restriction to participants diagnosed with T2DM.

  • A listed GLP-1 trial is cited as a gastric-bypass trial

    Minor

    Table 1 describes study 76 as comparing exenatide plus conventional therapy with conventional therapy. Its cited reference instead identifies a trial of Roux-en-Y gastric bypass surgery.

  • HbA1c units differ between the table and the results text

    Minor

    Table 1 labels its HbA1c column in mmol/mol, while the reported average HbA1c uses percent. The table values are presented on approximately the same numerical scale as the percentage result, leaving the column's stated unit inconsistent with the results text.

  • The longest-follow-up citation points to a 17-day trial

    Minor

    The text attributes the 156-week follow-up to study 66, but Table 1 lists study 66 as lasting 17 days. Table 1 assigns 156 weeks to study 69.

4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 7

  1. Li J, 2021, Effects and characteristics of liraglutide and its correlation with intestinal microflora in patients with type 2diabetes, Journal of Pathogen Biology, 16, 1325
  2. Jiang Z, 2020, Clinical trial of liraglutide in the treatment of patients with type 2 diabetes mellitus and non‐alcoholic fatty liver, Chin J Clin Pharmacol, 36, 400
  3. Sun N, 2020, Clinical trial of liraglutide injection combined with metformin tablets in the treatment of patients with type 2 diabetes mellitus and obesity, Chin J Clin Pharmacol, 36, 1453
  4. Zhao Z, 2020, Clinical trial of liraglutide combined with insulin injection in the treatment of patients with type 2 diabetes mellitus, Chin J Clin Pharmacol, 36, 2765
  5. Wang Q, 2020, Comparison between the effects of sitagliptin and liraglutide on blood glucose and cognitive function of patients with both type 2 diabetes mellitus and post‐stroke mild cognitive impairment, Int J Clin Exp Med, 13, 1219
  6. Pavithra D, 2019, A prospective randomized control study on effect of liraglutide on cardiovascular outcomes in type II diabetes mellitus, Drug Invention Today, 12, 2549
  7. Jian X, 2018, Clinical trial of liraglutide injection in the treatment of patients with overweight and obese type 2 diabetes mellitus complicated with microalbuminuria, Chin J Clin Pharmacol, 34, 2803

Cited by

Sorted by citations

Related

Authors
Ren, Y., Chen, Y., Zheng, W., Kong, W., Liao, Y., Zhang, J., Wang, M., & Zeng, T.
Affiliations
Wuhan Union Hospital (CN)
Corresponding author
Zeng, Tianshu
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2025-04-15
Volume
27
Issue
7
Pages
3607-3626
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.16366
OpenAlex
W4409463683
Semantic Scholar
ed84fb377cebc484f2e332afebfdb46eb4b6b6c9
Cited by
59
References
136
Citations by year
2026: 45 · 2025: 14
FWCI
7.96
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81974107, 82270909)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
GLP-1 receptor agonists, type 2 diabetes, inflammation, inflammatory markers, C-reactive protein, TNF-α, interleukin-6, IL-1β, leptin, adiponectin, plasminogen activator inhibitor-1, MCP-1, advanced glycation end products, anti-inflammatory activity
MeSH terms
Glucagon-Like Peptide-1 Receptor Agonists, C-Reactive Protein, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Inflammation, Biomarkers, Randomized Controlled Trials as Topic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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