{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:04:11Z","timestamp":1784567051160,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus and obesity, have recently attracted attention for their potential effects on periodontal tissues. This systematic review aimed to evaluate the current evidence regarding the relationship between GLP-1-based therapies and periodontal health, with particular emphasis on anti-inflammatory, osteogenic, and regenerative mechanisms. A comprehensive literature search of PubMed, Web of Science, and Embase databases identified 22 eligible studies, including in vitro, animal, and human investigations. The available evidence suggests that GLP-1RAs such as liraglutide and exendin-4 may attenuate periodontal inflammation, reduce alveolar bone loss, and enhance osteogenic differentiation of periodontal ligament and dental pulp stem cells through modulation of pathways including MAPK\/ERK, Wnt\/\u03b2-catenin, NF-\u03baB, and PKC\u03b22. Clinical observations additionally indicate a bidirectional relationship between periodontitis and incretin signalling, with periodontal therapy associated with increased systemic GLP-1 levels. However, the current evidence remains heterogeneous and is largely limited to preclinical and observational studies. Randomised clinical trials are required to determine the clinical efficacy and therapeutic relevance of GLP-1-based therapies in periodontitis management.<\/jats:p>","DOI":"10.3390\/ijms27146447","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:27Z","timestamp":1784564367000},"page":"6447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Relationship Between GLP-1-Based Therapies and Periodontal Health: A Systematic Review of Current Evidence and Future Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-5985","authenticated-orcid":false,"given":"Kacper","family":"Nijakowski","sequence":"first","affiliation":[{"name":"Department of Conservative Dentistry, Poznan University of Medical Sciences, 60-812 Pozna\u0144, Poland"},{"name":"Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4183","authenticated-orcid":false,"given":"Dawid","family":"Gruszczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, 60-355 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon","family":"\u0141acinik","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry, Poznan University of Medical Sciences, 60-812 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Zdrojewski","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry, Poznan University of Medical Sciences, 60-812 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7390-4316","authenticated-orcid":false,"given":"Livia","family":"Ottolenghi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0525-681X","authenticated-orcid":false,"given":"Marta","family":"Mazur","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Wellbeing, Health and Environmental Sustainability (BeSSA), Sapienza University of Rome, 02100 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barutta, F., Bellini, S., Durazzo, M., and Gruden, G. (2022). Novel Insight into the Mechanisms of the Bidirectional Relationship Between Diabetes and Periodontitis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010178"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/jcpe.12803","article-title":"An Update on the Evidence for Pathogenic Mechanisms That May Link Periodontitis and Diabetes","volume":"45","author":"Polak","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/jdi.12911","article-title":"Glucagon-like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Rational Drug Development","volume":"10","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R211","DOI":"10.1530\/EJE-19-0566","article-title":"Management of Endocrine Disease: Are All GLP-1 Agonists Equal in the Treatment of Type 2 Diabetes?","volume":"181","author":"Nauck","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/jper.70092","article-title":"GLP-1 Receptor Agonists: Bridging Diabetes, Obesity, and Periodontitis-A Scoping Review of Emerging Evidence","volume":"97","author":"Polymeri","year":"2026","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s13410-020-00879-4","article-title":"GLP1 Agonists beyond Glycemic Control\u2014Redefining Their Role","volume":"40","author":"Chowdhury","year":"2020","journal-title":"Int. J. Diabetes Dev. Ctries."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sawicka-Gutaj, N., Gruszczy\u0144ski, D., Nijakowski, K., Derwich-Rudowicz, A., Krenz, M., Kumar, A., Lu, P.-Y., and Rucha\u0142a, M. (2026). GLP-1 Agonists and Changes in Body Mass and Composition in Adults with Overweight or Obesity with or without Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Int. J. Obes.","DOI":"10.1038\/s41366-026-02088-1"},{"key":"ref_8","first-page":"473","article-title":"American Association of Clinical Endocrinology Consensus Statement: Algorithm for Management of Adults with Type 2 Diabetes\u20142026 Update","volume":"32","author":"Samson","year":"2026","journal-title":"Endocr. Pract. Off. J. Am. Coll. Endocrinol. Am. Assoc. Clin. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, J., Mei, A., Wei, Y., Li, C., Qian, H., Min, X., Yang, H., Dong, L., Rao, X., and Zhong, J. (2022). GLP-1 Receptor Agonist as a Modulator of Innate Immunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.997578"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rode, A.K.O., Buus, T.B., Mraz, V., Al-Jaberi, F.A.H., Lopez, D.V., Ford, S.L., Hennen, S., Eliasen, I.P., Klewe, I.V., and Gharehdaghi, L. (2022). Induced Human Regulatory T Cells Express the Glucagon-like Peptide-1 Receptor. Cells, 11.","DOI":"10.3390\/cells11162587"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jeong, N., Chuang, L.-H., and Ho, Y. (2025). Periodontitis and GLP-1 Pathways: A New Frontier in Oral-Systemic Health Connections\u2014A Scoping Review. Front. Clin. Diabetes Healthc., 6.","DOI":"10.3389\/fcdhc.2025.1679511"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/jcpe.13769","article-title":"Prevalence of Periodontitis in Dentate People between 2011 and 2020: A Systematic Review and Meta-Analysis of Epidemiological Studies","volume":"50","author":"Trindade","year":"2023","journal-title":"J. Clin. Periodontol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S159","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and Grading of Periodontitis: Framework and Proposal of a New Classification and Case Definition","volume":"89","author":"Tonetti","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/jre.13242","article-title":"Lipotoxicity: The Missing Link between Diabetes and Periodontitis?","volume":"59","author":"Sun","year":"2024","journal-title":"J. Periodontal Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s40496-021-00295-5","article-title":"What Are the Clinical and Systemic Results of Periodontitis Treatment in Obese Individuals?","volume":"8","author":"Dezonne","year":"2021","journal-title":"Curr. Oral Health Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1210\/clinem\/dgaa757","article-title":"Effect of Treatment of Periodontitis on Incretin Axis in Obese and Nonobese Individuals: A Cohort Study","volume":"106","author":"Suvan","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/s41366-018-0253-4","article-title":"Periodontitis Affects Glucoregulatory Hormones in Severely Obese Individuals","volume":"43","author":"Solini","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jre.13410","article-title":"Glucagon-Like Peptide 1 Receptor Agonists (GLP-1RAs) Improve Periodontal and Peri-Implant Health in Type 2 Diabetes Mellitus","volume":"60","author":"Ahmad","year":"2025","journal-title":"J. Periodontal Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1902\/jop.2015.150278","article-title":"Exenatide and Sitagliptin Decrease Interleukin 1\u03b2, Matrix Metalloproteinase 9, and Nitric Oxide Synthase 2 Gene Expression But Does Not Reduce Alveolar Bone Loss in Rats with Periodontitis","volume":"86","author":"Moraes","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1571","DOI":"10.20883\/medical.e1571","article-title":"Generative Artificial Intelligence in Scientific Publishing: Ethical Governance, Challenges, and Responsibilities","volume":"95","author":"Nijakowski","year":"2026","journal-title":"J. Med. Sci."},{"key":"ref_22","unstructured":"(2020, August 22). Study Quality Assessment Tools | NHLBI, NIH, Available online: https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools."},{"key":"ref_23","unstructured":"(2026, July 12). OCEBM Levels of Evidence. Available online: https:\/\/www.cebm.ox.ac.uk\/resources\/levels-of-evidence\/ocebm-levels-of-evidence."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20230692","DOI":"10.1515\/med-2023-0692","article-title":"Exendin-4 Regulates the MAPK and WNT Signaling Pathways to Alleviate the Osteogenic Inhibition of Periodontal Ligament Stem Cells in a High Glucose Environment","volume":"18","author":"Wang","year":"2023","journal-title":"Open Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8843310","DOI":"10.1155\/2020\/8843310","article-title":"Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis","volume":"2020","author":"Sawada","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12997","DOI":"10.1111\/cpr.12997","article-title":"Stromal Cell-Derived Factor-1\/Exendin-4 Cotherapy Facilitates the Proliferation, Migration and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells In Vitro and Promotes Periodontal Bone Regeneration In Vivo","volume":"54","author":"Liang","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101582","DOI":"10.1016\/j.mtbio.2025.101582","article-title":"PLGA\/HA Sustained-Release System Loaded with Liraglutide for the Treatment of Diabetic Periodontitis through Inhibition of Necroptosis","volume":"31","author":"Pang","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s11658-026-00867-2","article-title":"The Promoting Roles of GLP1R and GIPR in Stemness Maintenance and Multiple Lineage-Specific Differentiation of PDLSCs","volume":"31","author":"Shen","year":"2026","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.archoralbio.2018.03.014","article-title":"Exendin-4 Relieves the Inhibitory Effects of High Glucose on the Proliferation and Osteoblastic Differentiation of Periodontal Ligament Stem Cells","volume":"91","author":"Guo","year":"2018","journal-title":"Arch. Oral Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7639451","DOI":"10.1155\/sci\/7639451","article-title":"Exendin-4 Reduces Senescence of Inflammation-Induced Periodontal Ligament Stem Cells Through SIRT1\/Notch1 Signaling","volume":"2025","author":"Xu","year":"2025","journal-title":"Stem Cells Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"105801","DOI":"10.1016\/j.intimp.2019.105801","article-title":"Exendin-4 Regulates Wnt and NF-\u03baB Signaling in Lipopolysaccharide-Induced Human Periodontal Ligament Stem Cells to Promote Osteogenic Differentiation","volume":"75","author":"Liu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107495","DOI":"10.1016\/j.jdiacomp.2019.107495","article-title":"GLP-1 Inhibits PKC\u03b22 Phosphorylation to Improve the Osteogenic Differentiation Potential of hPDLSCs in the AGE Microenvironment","volume":"34","author":"Wang","year":"2020","journal-title":"J. Diabetes Complicat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/jre.12607","article-title":"The Effect of Liraglutide on the Proliferation, Migration, and Osteogenic Differentiation of Human Periodontal Ligament Cells","volume":"54","author":"Pang","year":"2019","journal-title":"J. Periodontal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103310","DOI":"10.1016\/j.jdent.2020.103310","article-title":"Liraglutide Regulates Bone Destruction and Exhibits Anti-Inflammatory Effects in Periodontitis In Vitro and In Vivo","volume":"94","author":"Zhang","year":"2020","journal-title":"J. Dent."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s13770-026-00801-9","article-title":"Liraglutide Promoted Osteogenic Differentiation of Dental Pulp Stem Cells via H3K18 Lactylation-Dependent DSPP Activation","volume":"23","author":"Li","year":"2026","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5160","DOI":"10.1111\/odi.14931","article-title":"The Effect and Mechanism of Liraglutide on the Biological Functions of BMSCs in Diabetic Patients","volume":"30","author":"Wang","year":"2024","journal-title":"Oral Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8260111","DOI":"10.1155\/2022\/8260111","article-title":"Therapeutic Potential of Liraglutide for Diabetes-Periodontitis Comorbidity: Killing Two Birds with One Stone","volume":"2022","author":"Yang","year":"2022","journal-title":"J. Diabetes Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e12091","DOI":"10.7717\/peerj.12091","article-title":"Transcriptome Analysis Reveals the Mechanism of Stromal Cell-Derived Factor-1 and Exendin-4 Synergistically Promoted Periodontal Ligament Stem Cells Osteogenic Differentiation","volume":"9","author":"Kang","year":"2021","journal-title":"PeerJ"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/jdi.12450","article-title":"Anti-Inflammatory Role of Glucose-Dependent Insulinotropic Polypeptide in Periodontitis","volume":"7","author":"Suzuki","year":"2016","journal-title":"J. Diabetes Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170974","DOI":"10.1016\/j.peptides.2023.170974","article-title":"Glucagon-like Peptide-1 Receptor Promotes Osteoblast Differentiation of Dental Pulp Stem Cells and Bone Formation in a Zebrafish Scale Regeneration Model","volume":"163","author":"Zhai","year":"2023","journal-title":"Peptides"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"178445","DOI":"10.1016\/j.ejphar.2025.178445","article-title":"Amelioration of D-Galactose-Induced Hyposalivation in Aging Rats by the GLP-1 Receptor Agonist Exendin-4","volume":"1011","author":"Jung","year":"2026","journal-title":"Eur. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mohamed, H.G., Idris, S.B., Mustafa, M., Ahmed, M.F., \u00c5str\u00f8m, A.N., Mustafa, K., and Ibrahim, S.O. (2015). Impact of Chronic Periodontitis on Levels of Glucoregulatory Biomarkers in Gingival Crevicular Fluid of Adults with and without Type 2 Diabetes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127660"},{"key":"ref_43","first-page":"101","article-title":"Effectiveness of Periodontal Treatment to Improve Glycemic Control: An Umbrella Review","volume":"60","author":"Minoli","year":"2023","journal-title":"Acta Diabetol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:57Z","timestamp":1784564397000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":43,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146447"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146447","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}