Progressive insulin secretory defects, due to either functional abnormalities of the pancreatic beta-cells or a reduction in beta-cell mass, are the cornerstone of type 2 diabetes. Incretin-based drugs hold the potential to improve glucose tolerance by immediate favorable effect on beta-cell physiology as well as by expanding or at least maintaining beta-cell mass, which may delay the progression of the disease. Long-term studies in humans are needed to elaborate on these effects.