Novel pharmacologic agents for type 2 diabetes

Endocrinol Metab Clin North Am. 2005 Mar;34(1):155-97. doi: 10.1016/j.ecl.2004.11.006.


After many decades of relative therapeutic stagnation since the initial discovery of insulin, followed by some modifications on its structure and only having sulfonylureas and biguanides for many years, the last decade has seen a surge in new therapeutic options for the management of diabetes. The results of the United Kingdom Prospective Diabetes Study and Kumamoto study indicate the need for aggressive glycemic control and the slow inexorable clinical deterioration associated with type 2 diabetes overtime. The propensity for weight gain and hypoglycemia are the two major limitations that subcutaneous insulin and sulfonylureas have been particularly prone to. The newer antidiabetic medications and those on the horizon attempt to address these limitations. GLP-1 agonists and the DPP-IV inhibitors exploit the innate incretin system to improve glycemia while promoting satiety and weight management. Like GLP-1 related compounds, pramlintide offers the potential to address postprandial hyperglucagonemia associated with type 2 diabetes only limited by the multiple injections and gastrointestinal side effects. The glitazars offer the hope ofa new approach to diabetes care addressing not just glycemia, but dyslipidemia and other components of the metabolic syndrome, though the side effect profile remains a major unknown. The INGAP peptide represents the holy grail of diabetes care as it offers the potential of a new paradigm: that of islet regeneration and potential for a cure. But at this stage, with no human data available, it remains highly speculative. Beyond these and other novel agents being developed to meet the challenge of the worldwide epidemic of diabetes, the central place of insulin in diabetes care cannot be forgotten. In view of this the continued efforts of improvement in insulin delivery, kinetics and action have spurred such innovations as the various inhaled insulins and new insulin analogues. There is cause for guarded optimism and excitement about the years ahead. There is reason to expect that despite the growing burden of diabetes worldwide, we will be better equipped to manage it and its comorbidities and prevent its onset and possibly even cure it.

Publication types

  • Review

MeSH terms

  • Amyloid / therapeutic use
  • Antigens, Neoplasm / therapeutic use
  • Biomarkers, Tumor / therapeutic use
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4 / therapeutic use
  • Glucagon / agonists*
  • Glucagon / therapeutic use
  • Glucagon-Like Peptide 1
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / analogs & derivatives*
  • Insulin / therapeutic use
  • Insulin Detemir
  • Insulin, Long-Acting
  • Islet Amyloid Polypeptide
  • Lectins, C-Type / therapeutic use
  • Pancreatitis-Associated Proteins
  • Peptide Fragments / agonists*
  • Peptide Fragments / therapeutic use
  • Polymers / therapeutic use
  • Protein Precursors / agonists*
  • Protein Precursors / therapeutic use
  • Thiazolidinediones / therapeutic use


  • Amyloid
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Exubera
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Islet Amyloid Polypeptide
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • Peptide Fragments
  • Polymers
  • Protein Precursors
  • REG3A protein, human
  • Thiazolidinediones
  • hexyl-insulin monoconjugate 2
  • Insulin Detemir
  • Glucagon-Like Peptide 1
  • Glucagon
  • pramlintide
  • Dipeptidyl Peptidase 4