The physiologic role of incretin hormones: clinical applications.
Treatment of patients with type 2 diabetes mellitus (T2DM) traditionally has involved a progression of phases, from conventional lifestyle interventions and monotherapy, to combination therapy involving oral agents, to insulin initiation and its use either alone or with oral pharmacotherapy. Currently, the need for antidiabetic therapies with fewer adverse effects (eg, weight gain, reduced rates of hypoglycemia) is unmet. In addition, most treatments fail to adequately control postprandial hyperglycemia. Traditional options have generally been directed at the "insulin demand" aspect and have targeted insulin secretion or insulin resistance in peripheral tissues. Only recently have agents been available to address the "glucose supply" aspect that leads to fasting hyperglycemia in patients with T2DM. Incretin-based therapies, however, address both aspects. Two classes of incretin-directed therapies are available and work by either increasing endogenous levels of glucagon-like peptide-1 (GLP-1) (ie, dipeptidyl peptidase-4 inhibitors) or by mimicking the activity of endogenous GLP-1 (ie, GLP-1 agonists). These therapies treat the key metabolic abnormalities associated with T2DM but do so with reduced rates of hypoglycemia and do not promote weight gain as compared with conventional therapies.
Cefalu
William T
WT
Pennington Biomedical Research Center in Baton Rouge, Louisiana, LA, USA. william.cefalu@pbrc.edu
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004151:Dipeptides / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000096:biosynthesis / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D054795:Incretins / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use
D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D010880:Piperidines; D011719:Pyrazines; D014230:Triazoles; D014498:Uracil; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C502994:saxagliptin; C520853:alogliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate