Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Left Ventricular Global Longitudinal Strain in Adults with Type 2 Diabetes Mellitus: A Systematic Review

Background: Type 2 diabetes mellitus (T2DM) is associated with subclinical myocardial dysfunction, which may occur despite preserved left ventricular ejection fraction. Left ventricular global longitudinal strain (LV GLS) is a sensitive marker of early systolic impairment and may detect subtle changes in myocardial function before conventional echocardiographic parameters become abnormal. The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on LV GLS in adults with T2DM remains incompletely defined. Objective: To synthesize the available evidence on the effects of SGLT2i therapy on LV GLS or LV strain in adults with T2DM. Methods: Original full-text human studies evaluating SGLT2i therapy in adults with T2DM and reporting LV GLS or LV strain were included. LV GLS was assessed primarily by speckle-tracking echocardiography, while one study used cardiac magnetic resonance feature-tracking. Reviews, conference abstracts, protocols, animal-only studies, and studies without LV strain assessment were excluded. Risk of bias was assessed using RoB 2 for randomized studies and ROBINS-I for non-randomized studies. Results: Twenty-six studies involving more than 2300 participants were included. The studies evaluated dapagliflozin, empagliflozin, ertugliflozin, canagliflozin, or mixed SGLT2i regimens across heterogeneous clinical populations, including patients with preserved ejection fraction, pre-heart failure, diabetes-related cardiomyopathy, chronic heart failure, coronary artery disease, hypertension, non-alcoholic fatty liver disease, and cardio-oncology risk. Most observational and before–after studies reported favorable changes in LV GLS after SGLT2i therapy, whereas randomized and controlled studies showed more variable findings. Several studies also reported improvements in LV remodeling, diastolic function, left atrial function, myocardial work indices, NT-proBNP, cardiometabolic parameters, or epicardial adipose tissue thickness. However, the certainty of evidence was limited by methodological heterogeneity, differences in comparator groups, variable follow-up duration, non-standardized imaging protocols, and risk of bias, particularly in non-randomized and single-arm studies. Conclusions: SGLT2i therapy may be associated with favorable changes in LV GLS in adults with T2DM, suggesting a potential beneficial effect on subclinical left ventricular systolic function. However, current evidence does not definitively establish a consistent treatment effect across all populations. Larger randomized controlled trials with standardized strain imaging protocols, predefined LV GLS endpoints, and clinically relevant follow-up are needed to determine whether SGLT2i-related improvements in LV GLS reflect true myocardial benefit and translate into improved cardiovascular outcomes.