Emerging incretin based therapies for type 2 diabetes: incretin mimetics and DPP-4 inhibitors.
Type 2 diabetes is a chronic disease characterized by impaired insulin action, progressive beta cell dysfunction as well as abnormalities in pancreatic alpha cell function and postprandial substrate delivery. These pathophysiologic defects result in both persistent and progressive hyperglycemia, resulting in increased risk of both microvascular and cardiovascular complications. Traditional treatments for type 2 diabetes have focused on impaired insulin secretion and insulin resistance. These strategies are typically used in a stepwise manner: employing oral glucose lowering agents, followed by insulin therapy. This traditional approach fails to address the progressive decline in beta cell function. Moreover, these therapies are often associated with weight gain in overweight or obese patients with type 2 diabetes. Both exogenous insulin and insulin secretagogues are associated with an increased risk of hypoglycemia. Recently, new treatments that leverage the glucoregulatory effects of incretin hormones, such as glucagon like peptide 1 have been introduced. Both incretin mimetics and DPP-4 inhibitors address both the underlying pathophysiology and overcome several of the limitations of established therapies by providing improvements in glycemia, and control of body weight with minimal risk of hypoglycemia.
Stonehouse
Anthony
A
Amylin Pharmaceuticals, Inc., 9360 Towne Centre Dr., San Diego, CA 92121, USA. anthony.stonehouse@amylin.com
Okerson
Ted
T
Kendall
David
D
Maggs
David
D
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D054795:Incretins / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D008019:Life Style; D000069450:Liraglutide; D009765:Obesity / Q000453:epidemiology; D050177:Overweight / Q000453:epidemiology; D010455:Peptides / Q000627:therapeutic use; D015995:Prevalence; D014688:Venoms / Q000627:therapeutic use
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide