Continual evolution of type 2 diabetes: an update on pathophysiology and emerging treatment options

Abstract

Diabetes is a complex and progressive disease that has a major societal and economic impact. The most common form of diabetes, type 2 diabetes mellitus (T2DM), is a multifactorial disease, the pathophysiology of which involves not only the pancreas but also the liver, skeletal muscle, adipose tissue, gastrointestinal tract, brain, and kidney. Novel therapies with mechanisms of action that are different from most existing drugs are emerging. One such class consists of compounds that inhibit renal sodium-glucose cotransporter 2, which is responsible for the bulk of glucose reabsorption by the kidneys. This new class of compounds improves glycemic control independently of insulin and promotes weight reduction, providing an additional tool to treat patients with T2DM. This review discusses the underlying pathophysiology of T2DM, clinical guidelines, and available and emerging treatment options, with particular emphasis on sodium-glucose cotransporter 2 inhibitors.

Keywords: diabetes; hyperglycemia; oral antidiabetic therapies; pharmacotherapy; sodium-glucose cotransporter 2.

Figure 1

Multiorgan and tissue pathophysiology of type 2 diabetes. Notes: Adapted with permission from DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–795. Abbreviations: FFA, free fatty acids; GLP-1, glucagon-like peptide-1.

Figure 2

General recommendations for the treatment of type 2 diabetes from the American Diabetes Association/European Association for the Study of Diabetes. Notes: ^aOrder of drugs does not denote any specific preference; ^busually basal insulin. Copyright © 2009. American Diabetes Association. Adapted with permission from Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140–149. Abbreviations: DPP-4i, dipeptidyl peptidase-4 inhibitor; GLP-1 RA, glucagon-like peptide-1 receptor agonist; A_1C, glycated hemoglobin; Met, metformin; SGLT2i, sodium-glucose co-transporter 2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione.