Current issues in the treatment of type 2 diabetes. Overview of newer agents: where treatment is going

Am J Med. 2010 Mar;123(3 Suppl):S38-48. doi: 10.1016/j.amjmed.2009.12.008.


Impaired insulin secretion (beta-cell), increased hepatic glucose production (liver), and decreased peripheral (muscle) glucose utilization constitute the traditional primary defects responsible for the development and progression of type 2 diabetes mellitus. beta-Cell failure, ultimately leading to decreased insulin secretion, is now known to occur much earlier in the natural history of type 2 diabetes than originally believed. Additionally, a better understanding of the pathophysiology of type 2 diabetes reveals other etiologic mechanisms beyond the classic triad, now referred to as the ominous octet. In addition to the beta-cell, liver, and muscle, other pathogenic mechanisms include adipocyte insulin resistance (increased lipolysis), reduced incretin secretion/sensitivity (gastrointestinal), increased glucagon secretion (alpha-cell), enhanced glucose reabsorption (kidney), and central nervous system insulin resistance resulting from neurotransmitter dysfunction (brain). Currently, the management of type 2 diabetes focuses on glucose control via lowering of blood glucose (fasting and postprandial) and hemoglobin A(1c). However, the goal of therapy should be to delay disease progression and eventual treatment failure. Treatment should target the known pathogenic disturbances of the disease (i.e., reducing the deterioration of beta-cell function and improving insulin sensitivity). In recent years, treatment strategies have focused on the development of novel therapeutic options that affect many of the defects contributing to type 2 diabetes and that provide durable glucose control through a blunting of disease progression. Optimal management of type 2 diabetes should include early initiation of therapy using multiple drugs, with different mechanisms of action, in combination.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / physiopathology
  • Diabetic Angiopathies / prevention & control
  • Humans
  • Hyperglycemia / drug therapy
  • Hyperglycemia / physiopathology
  • Hypoglycemic Agents / therapeutic use*
  • Incretins / physiology
  • Insulin Resistance / physiology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology
  • Prediabetic State / drug therapy
  • Prediabetic State / physiopathology


  • Hypoglycemic Agents
  • Incretins