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Systemic Glucose-Lowering Therapies and Periodontal and Peri-Implant Outcomes in Adults With Type 2 Diabetes Mellitus: A Systematic Review

Year: 2026

Type: review

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.

Source: Cureus

DOI: 10.7759/cureus.117011