To date, the most meaningful class effect of SGLT-2 inhibitors appears to be that on HF hospitalization for the following reasons: (1) the reduced risk for HF hospitalization is > 25% in every CVOT published until now (range 27–39%); (2) there is a complete absence of heterogeneity (I2 = 0%, P = 0.98) in the meta-analysis; (3) the confidence intervals of the HR are very close to the point estimate; and (4) the reduced risk of hospitalization for HF is significant in every CVOTs. The gene discussed is SLC5A2; the disease is hydrops fetalis.