Abstract Background Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic regimens linked with a significant reduction in the risk for surrogate cardiovascular and renal outcomes. Specific patient populations, for example subjects with heart failure with reduced ejection fraction (HFrEF), also benefit from this drug class, regardless the presence of T2DM. Left ventricular (LV) hypertrophy is a strong, independent predictor of cardiovascular morbidity and mortality; left atrial volume index (LAVI), an indicator of severity of LV diastolic dysfunction and filling properties, has been shown to predict “hard” cardiovascular outcomes among patients with T2DM, while it might predict the recovery of left ventricular ejection fraction in patients with HFrEF. Purpose We sought to determine the effect of SGLT-2 inhibitors on the above indices, in order to evaluate additional cardioprotective mechanisms of this drug class. Methods We searched 2 major electronic databases (PubMed and Cochrane/CENTRAL) along with grey literature sources for parallel-group RCTs investigating the effect of SGLT-2 inhibitors compared to placebo or active control on LV mass, LV mass index (LVMI) and LAVI, evaluated either by TTE or CMR, on adult patients regardless the presence of T2DM or HF. Results After screening the potentially eligible records, 9 studies were included in our analysis with a total of 843 patients. Treatment with SGLT-2 inhibitors compared to placebo or active control leads to a statistically significant decrease in LV mass by 6.01 g (95% CI −11.33 to −0.69, I2=76%) (Figure 1a). A significant decrease in LVMI by 2.61 g/m2 was observed (MD=−2.61, 95% CI −4.94 to −0.29, I2=65%) (Figure 1b). Of note, the effect on LAVI was marginally non-significant (MD=−1.51 ml/m2, 95% CI −3.05 to 0.03, I2=0%) (Figure 1c). Subgroup analysis for patients with HFrEF demonstrated a non-significant reduction in LV mass (MD=−11.72 g, 95% CI −30.61 to 7.16, I2=90%) and in LVMI (MD=−6.28 g/m2, 95% CI −30.61 to 0.25, I2=80%) (Figure 2a and 2b). Conclusions SGLT-2 inhibitors demonstrate a clear benefit on LV mass and LVMI, regardless of diabetes status, while a marginally non-significant effect is observed on LAVI. These results provide further insights into the cardioprotective mechanisms mediated by this drug class, besides those already established. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2
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