In contrast to β-cell-directed therapies, insulin-sensitizing agents, such as thiazolidinediones (TZD) and, to a lesser extent, metformin, can delay the loss of islet β-cell mass in rodent diabetes models and promote recovery of β-cell function in human T2D, despite primarily functioning to improve insulin signaling in peripheral tissues and thus indirectly impacting β-cell function [195,202,203]. Here, INS is linked to type 2 diabetes mellitus.