Pharmacological targeting of PFKFB3 to abort survival of dysfunctional “loser” β-cells holds a promise to change and prevent deterioration of early T2D trajectory given that at this stage both the prevalence of “loser” β-cells and “loser” β-cell survival selectively depend on PFKFB3. This evidence concerns the gene PFKFB3 and type 2 diabetes mellitus.