The noncommunicable disease of diabetes mellitus has reached epidemic proportions, and it knows no geographic boundaries (Turner 2014). Diabetes, a chronic disorder characterized by elevations in both basal and postprandial (post-meal) glucose levels, is associated with a two- to fourfold increased risk of cardiovascular disease and a threefold increased risk of mortality (Meigs 2003). There are two major forms of diabetes, type 1 and type 2. The typical age of onset of type 1 diabetes is in childhood. This form is also known as insulin-dependent diabetes since patients do not produce enough insulin for healthy function: multiple daily injections of insulin (i.e., exogenous insulin) are required to maintain life, and strict dietary rules, planned physical activity, and daily home glucose tests are also necessary.

The characterization of type 2 diabetes has changed over recent years. Previously used terms such as non-insulin-dependent diabetes and adult-onset diabetes are no longer appropriate: some individuals with type 2 diabetes do require insulin, and children now have this form of the disease. It is characterized by decreased insulin secretion and insulin resistance, a condition in which insulin is not able to carry out its functions effectively, i.e., it cannot decrease plasma glucose levels via suppression of hepatic glucose and stimulation of glucose use in skeletal muscle and adipose tissue.

As one example from a country in the Western world, the US National Diabetes Statistics Report, 2014, observed that in 2012, 29.1 million Americans (9.3 %) had diabetes and that 86 million individuals aged 20 years and older had prediabetes: the respective figures for just 2 years earlier were 25.8 million (8.3 %) and 79 million (CDC 2014). Type 1 diabetes has long been a disease observed in pediatric populations, but, as noted a few moments ago, the same is now true for type 2 diabetes. The prevalence of pediatric type 1 diabetes in the USA increased from 1.48 to 1.93 per 1000 from 2001 to 2009: when adjusted for completeness of ascertainment, these figures represent a 21.1 % increase (Dabelea et al. 2014). Although it is true that the absolute number of pediatric patients with type 2 diabetes is less than for type 1 diabetes, the rate of increase is greater: the estimated US prevalence increased from 0.34 to 0.46 per 1000 across the same time span, representing a 30.5 % increase (Dabelea et al. 2014).

Now consider a regional example outside the Western world. Close to 20 % of all adults in the world with diabetes live in the Southeast Asia region. As the worldwide figure is estimated to approach 600 million by 2035, the number of people with diabetes in Southeast Asia is estimated to increase to 123 million (International Diabetes Federation 2013). It is extremely concerning from a global public health perspective that most people with diabetes live in low- and middle-income countries; these countries will see the greatest increase over the next two decades (Whiting et al. 2011). The life expectancy of a patient with type 2 diabetes is likely to be reduced by up to 10 years as a result of this condition (Diabetes in the UK Report 2010), a dramatic statistic driven to a large extent by increased risk of heart disease, renal disease, and stroke. Quality as well as quantity of life can also be seriously affected given the additional burdens of nervous system damage, blindness, and lower-limb amputation.

When first-line interventions addressing a patient’s dietary and exercise habits have failed to prevent progression to diabetes, initiation of pharmaceutical regimens becomes necessary (an appropriate diet and appropriate levels of exercise should certainly be maintained as adjunctive therapy). At the time of writing this chapter, there are 12 classes of antidiabetic drugs approved in the USA for adults with type 2 diabetes: insulins, biguanides, second-generation sulfonylureas, glinides, thiazolidinediones, α-glucosidase inhibitors, DPP-4 inhibitors, GLP-1 agonists, SGLT2 inhibitors, bile acid sequestrants, dopamine agonists, and amylin analogues. While it may initially appear that this array of currently approved drugs comprises a robust list, the continuing medical need for additional pharmaceutical agents is well captured by the European Medicines Agency’s (EMA’s) guideline addressing clinical investigation of medicinal products in the treatment or prevention of diabetes, which comments as follows (EMA 2012):

Glucose control in type 2 diabetes deteriorates progressively over time, and, after failure of diet and exercise alone, needs on average a new intervention with glucose-lowering agents every 3–4 years in order to obtain/retain good control.

That is, a patient’s drug regimen becomes insufficient over several years, meaning that an additional drug will be added. When this happens, the drugs the patient is already taking are often kept as they still have a beneficial effect, but their effect alone is not great enough to counteract disease progression. A constant provision of new drugs is therefore needed. Accordingly, it is encouraging to report that new drugs within various classes continue to be developed and that there are multiple new classes of drugs being developed, including PPAR agonists/modulators (PPAR-α agonists, PPAR-δ agonists, PPAR-α/δ agonists, PPAR-δ/γ agonists, PPAR-α/γ co-agonists, and PPAR-α/δ/γ pan-agonists), glucokinase activators, C-C chemokine receptor type 2 antagonists, IL-1 modulators, G-protein-coupled receptor agonists, apical sodium-dependent bile acid transporter inhibitors, and 11-beta-HSD1 inhibitors (see Mittermayer et al. 2015).