Aim <p>This study aimed to evaluate the risk of doxorubicin-induced cardiotoxicity in newly diagnosed breast cancer patients with type 2 diabetes receiving dapagliflozin in addition to metformin, using echocardiographic methods, and to investigate the potential cardioprotective effects of dapagliflozin.</p> Materials and methods <p>In this prospective observational study, a total of 60 newly diagnosed breast cancer patients with type 2 diabetes were enrolled. Thirty patients who had been treated with metformin and subsequently received dapagliflozin in addition to metformin during doxorubicin therapy constituted the dapagliflozin group. The non-dapagliflozin group consisted of 30 patients who, while continuing metformin, were initiated on another oral antidiabetic agent (excluding dapagliflozin) alongside doxorubicin therapy. N-terminal pro-B type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) were measured at baseline and at the 3rd month of treatment. Between-group baseline characteristics were compared using the independent samples t-test for continuous variables. Within-group changes from baseline to 3 months were analyzed with paired t-tests. Between-group comparisons of 3-month outcomes and changes (ΔLVEF, ΔLVGLS, ΔNT-proBNP) were also conducted using independent samples t-tests. To evaluate the independent effect of dapagliflozin on LVGLS, multivariable linear regression analysis was performed. Model fit was reported with adjusted R², F-statistics and 95% confidence intervals.</p> Results <p>In the non-dapagliflozin group, LVEF and NT-proBNP levels showed no significant differences between baseline and post-treatment; however, LVGLS values significantly deteriorated. In contrast, the dapagliflozin group demonstrated a significant increase in LVEF (− 2.000 [95% CI − 2.392, − 1.608]) and LVGLS (+ 1.367 [95% CI + 1.159, + 1.574]), as well as a marked reduction in NT-proBNP levels (+ 64.933 [95% CI + 57.902, + 71.964]) after 3 months of treatment (<i>p</i> &lt; 0.001). At the third month, the dapagliflozin group exhibited significantly better LVGLS (+ 2.133 [95% CI + 1.346, + 2.921]) and lower NT-proBNP levels (+ 57.000 [95% CI + 28.302, + 85.698]) compared with the non-dapagliflozin group (<i>p</i> &lt; 0.001). Multivariable linear regression analysis confirmed that dapagliflozin use was independently associated with significant improvement in LVGLS at 3 months.</p> Conclusion <p>In conclusion, dapagliflozin was associated with more favorable short-term surrogate changes in LVGLS and NT-proBNP during doxorubicin therapy. The favorable changes observed in LVEF, LVGLS, and NT-proBNP parameters suggest that dapagliflozin may be considered a potential cardioprotective agent and incorporated into preventive strategies against chemotherapy-related cardiotoxicity in diabetic patients. These hypothesis-generating findings require confirmation in larger randomized trials powered for clinical endpoints with longer follow-up.</p> Clinical trial registration <p>Not applicable.</p>