Association of tirzepatide versus Glucagon-Like Peptide-1 receptor agonists with oral and periodontal outcomes in patients with type 2 Diabetes: A Global propensity Score-Matched cohort study.

AIMS: To evaluate the association between tirzepatide and recorded oral and periodontal outcomes compared with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with T2DM receiving tirzepatide or GLP-1RAs between May 2022 and May 2025 underwent 1:1 propensity score matching using baseline characteristics assessed during the preceding year. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality and oral and periodontal outcomes during 1-year follow-up. Additional analyses included subgroup, extended follow-up, active-comparator, composite-outcome, and E-value analyses. RESULTS: After matching, each cohort included 97,993 patients. Tirzepatide was associated with lower risks of mortality (HR 0.69, 95% CI 0.59-0.80), periodontitis (0.70, 0.57-0.86), tooth extraction (0.89, 0.84-0.94), peri-implant complications (0.61, 0.52-0.70), periodontal procedures (0.89, 0.85-0.94), and oral or maxillofacial infections (0.70, 0.62-0.79). The composite oral/periodontal outcome was also lower with tirzepatide (HR 0.87, 95% CI 0.84-0.91), with directionally consistent findings across additional analyses. CONCLUSIONS: Tirzepatide was associated with lower risks of recorded oral and periodontal outcomes than GLP-1RAs. Given the low recorded event rates and limitations of retrospective EHR data, these associations require confirmation in prospective studies with systematic dental assessments.