INS and type 2 diabetes mellitus: Metformin, a common treatment for T2D acting on the liver to reduce glucose production, has also been shown to have a direct effect on β-cells and islets to increase viability and function.38,39 Exendin-4 is a GLP-1 receptor agonist that can directly increase insulin secretion and proliferation40 while NaS is an anti-inflammatory agent that has also been shown to have direct, positive effects on islets.41 Thus, while this combination of drugs is not routinely used in patients, each of the drugs acts via a different mechanism to protect β-cells.