OBJECTIVE: Evaluate the effect of medications and medication changes during the Diabetes and Periodontal Therapy Trial (DPTT) on the primary study outcome, namely, change in hemoglobin A1c (HbA1c) at 6months following baseline. METHODS: The DPTT set strict criteria for changes in diabetes medications. Medication change was defined as: change in dose of any 1 oral hypoglycemic agent by more than two-fold, change in dose of insulin of >10% and/or addition or subtraction of an oral hypoglycemic agent, insulin or non-insulin injectable agents. Comparisons between the treatment (non- surgical periodontal therapy) and control (no therapy) groups used t-tests for continuous variables and chi-square tests for categorical variables, including DPTT defined diabetes medication changes between baseline (BL) and 3month visits and 3- and 6-month visits. Changes in HbA1c were compared across the four medication change categories using ANOVA models, overall and for each treatment group separately. RESULTS: Baseline medication use was similar between the treatment groups (p>0.40), as were medication changes between BL- 3month visits and 3 and 6month visits (p=0.58). Participants with higher BL HbA1c (>8%) and those taking insulin at BL were more likely to have a change in medication (p=0.03). CONCLUSIONS: The DPTT had the most rigorous definition of medication changes and medication monitoring of any trial in this field to date. The absence of a significant difference in medication changes between treatment groups may suggest that such changes did not play a role in the negative outcome of the DPTT.