Objective: The cardiovascular effects of sodium–glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors have attracted increasing interest in patients with type 2 diabetes mellitus. This study aimed to compare the time-dependent effects of empagliflozin and linagliptin on left ventricular diastolic function and global longitudinal strain (GLS).

Methods: This prospective longitudinal study included 350 patients with type 2 diabetes mellitus treated with empagliflozin (n = 200) or linagliptin (n = 150). Transthoracic echocardiography and speckle-tracking strain analysis were performed at baseline, 1 month, and 6 months. Diastolic function was evaluated using septal e′ velocity, E/e′ ratio, isovolumetric relaxation time (IVRT), and mitral E-wave deceleration time. Longitudinal changes were analyzed using linear mixed-effects models including treatment group,
time, and group × time interaction.

Results: Diastolic function parameters improved significantly over time in both groups (all
P < .001). At follow-up, HbA1c levels decreased in both groups, with comparable glycemic control achieved at 6 months. Significant group × time interactions were observed for septal e′ velocity, E/e′ ratio, and IVRT (all P < .001). These findings remained consistent after adjustment for baseline differences. At 6 months, empagliflozin was associated
with greater improvement in septal e′ velocity and IVRT, whereas linagliptin resulted in a more pronounced reduction in the E/e′ ratio. Although GLS improved in both groups, its temporal pattern differed significantly between treatments (P < .001).

Conclusion: Empagliflozin and linagliptin exert distinct effects on left ventricular diastolic function and myocardial deformation in type 2 diabetes mellitus. Empagliflozin appears to provide earlier improvement in diastolic relaxation and GLS, whereas linagliptin may have a greater effect on filling pressures. These findings should be interpreted cautiously and considered hypothesis-generating; confirmation in randomized controlled trials is required to determine their clinical relevance.