Systemic Glucose-Lowering Therapies and Periodontal and Peri-Implant Outcomes in Adults With Type 2 Diabetes Mellitus: A Systematic Review.
8 affiliations
- 1Department of Nephrology, Jazan Health Cluster, Jazan, SAU.
- 2Clinical Pharmacy Program, College of Health Sciences, Taibah University, Madinah, SAU.
- 3College of Medicine, Al-Baha University, Al-Baha, SAU.
- 4Faculty of Medicine, Tabuk University, Tabuk, SAU.
- 5College of Medicine, Majmaah University, Majmaah, SAU.
- 6College of Medicine, Taif University, Taif, SAU.
- 7Faculty of Dentistry, Jazan University, Jazan, SAU.
- 8Faculty of Medicine, Jazan University, Jazan, SAU.
Abstract
Type 2 diabetes mellitus (T2DM) and periodontitis are bidirectionally linked. Systemic glucose-lowering drug classes differ in their extra-glycaemic effects on inflammation and bone, which could plausibly modify periodontal and peri-implant health; however, this evidence has not been synthesised across drug classes. We conducted a systematic review and evidence gap map (EGM), with sodium-glucose cotransporter-2 (SGLT2) inhibitors examined as a pre-specified evidence gap. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus were searched and cross-checked against the Consensus academic corpus. Eligible studies enrolled adults with T2DM, evaluated a systemic glucose-lowering drug as the exposure, and reported a periodontal or peri-implant outcome. Studies of local drug delivery and periodontal therapy aimed at improving glycaemic control were excluded from the systematic-review layer; all study designs, including preclinical studies, were charted in the EGM. Risk of bias was assessed using the Cochrane risk-of-bias 2 (RoB 2) tool and the Newcastle-Ottawa Scale. Four studies were included: one randomised controlled trial and three observational studies. These comprised a trial of a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin) added to metformin, which reported improvements in probing depth, clinical attachment level, bleeding on probing, and alveolar bone density; a cohort study comparing peri-implant marginal bone loss among users of glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), metformin, and insulin, with the least bone loss observed among glucagon-like peptide-1 receptor agonist users; a large pharmacoepidemiological cohort evaluating DPP-4 inhibitor exposure; and a cross-sectional survey of glucagon-like peptide-1 receptor agonist users. Meta-analysis was not feasible because of substantial heterogeneity. The EGM, comprising eight drug classes and six outcome domains, showed that evidence was concentrated in glucagon-like peptide-1 receptor agonists and metformin and was almost entirely preclinical; the only high-level evidence cell was represented by a single DPP-4 inhibitor randomised controlled trial, while SGLT2 inhibitors constituted a complete evidence gap across all outcome domains. Based on the four included studies, human evidence linking systemic glucose-lowering therapy with periodontal outcomes in adults with T2DM is sparse, heterogeneous, and of low certainty, with weak signals favouring incretin-based therapies. SGLT2 inhibitors remain entirely unstudied in this context despite biological plausibility. The EGM identifies specific, high-value priorities for future randomised trials and prospective cohort studies.
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BibTeX
@article{hakami2026systemic,
title = {{Systemic Glucose-Lowering Therapies and Periodontal and Peri-Implant Outcomes in Adults With Type 2 Diabetes Mellitus: A Systematic Review.}},
author = {Abadi A Hakami and Lina A Alamri and Shahad A Alghamdi and Hala T Alanazi and Ali A Alqahtani and Waleed K Almutairi and Turki R Alzahrani and Fatma M Toonisi and Maram A Alsamti and Abdulmalik M Mossa and Amirah Y Hakami},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.117011},
url = {https://europepmc.org/article/MED/42948780},
note = {CC BY},
}
RIS
TY - JOUR
TI - Systemic Glucose-Lowering Therapies and Periodontal and Peri-Implant Outcomes in Adults With Type 2 Diabetes Mellitus: A Systematic Review.
AU - Abadi A Hakami
AU - Lina A Alamri
AU - Shahad A Alghamdi
AU - Hala T Alanazi
AU - Ali A Alqahtani
AU - Waleed K Almutairi
AU - Turki R Alzahrani
AU - Fatma M Toonisi
AU - Maram A Alsamti
AU - Abdulmalik M Mossa
AU - Amirah Y Hakami
PY - 2026
DA - 2026/09/27
JO - Cureus
DO - 10.7759/cureus.117011
UR - https://europepmc.org/article/MED/42948780
AB - Type 2 diabetes mellitus (T2DM) and periodontitis are bidirectionally linked. Systemic glucose-lowering drug classes differ in their extra-glycaemic effects on inflammation and bone, which could plausibly modify periodontal and peri-implant health; however, this evidence has not been synthesised across drug classes. We conducted a systematic review and evidence gap map (EGM), with sodium-glucose cotransporter-2 (SGLT2) inhibitors examined as a pre-specified evidence gap. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus were searched and cross-checked against the Consensus academic corpus. Eligible studies enrolled adults with T2DM, evaluated a systemic glucose-lowering drug as the exposure, and reported a periodontal or peri-implant outcome. Studies of local drug delivery and periodontal therapy aimed at improving glycaemic control were excluded from the systematic-review layer; all study designs, including preclinical studies, were charted in the EGM. Risk of bias was assessed using the Cochrane risk-of-bias 2 (RoB 2) tool and the Newcastle-Ottawa Scale. Four studies were included: one randomised controlled trial and three observational studies. These comprised a trial of a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin) added to metformin, which reported improvements in probing depth, clinical attachment level, bleeding on probing, and alveolar bone density; a cohort study comparing peri-implant marginal bone loss among users of glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), metformin, and insulin, with the least bone loss observed among glucagon-like peptide-1 receptor agonist users; a large pharmacoepidemiological cohort evaluating DPP-4 inhibitor exposure; and a cross-sectional survey of glucagon-like peptide-1 receptor agonist users. Meta-analysis was not feasible because of substantial heterogeneity. The EGM, comprising eight drug classes and six outcome domains, showed that evidence was concentrated in glucagon-like peptide-1 receptor agonists and metformin and was almost entirely preclinical; the only high-level evidence cell was represented by a single DPP-4 inhibitor randomised controlled trial, while SGLT2 inhibitors constituted a complete evidence gap across all outcome domains. Based on the four included studies, human evidence linking systemic glucose-lowering therapy with periodontal outcomes in adults with T2DM is sparse, heterogeneous, and of low certainty, with weak signals favouring incretin-based therapies. SGLT2 inhibitors remain entirely unstudied in this context despite biological plausibility. The EGM identifies specific, high-value priorities for future randomised trials and prospective cohort studies.
SN - 2168-8184
ER -