Incretin mimetics and dipeptidyl peptidase-4 inhibitors: innovative treatment therapies for type 2 diabetes.
The prevalence of diabetes and impaired glucose tolerance is predicted to dramatically increase over the next two decades. Clinical therapies for type 2 diabetes mellitus (T2DM) have traditionally included lifestyle modification, oral anti-diabetic agents, and ultimately insulin initiation. In this report, we review the clinical trial results of two innovative T2DM treatment therapies that are based on the glucoregulatory effects of incretin hormones. Incretin mimetics are peptide drugs that mimic several of the actions of glucagon-like peptide-1 (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients with T2DM. Additionally, incretin mimetics lower postprandial and fasting glucose, suppress elevated glucagon release, and are associated with progressive weight reduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. Clinical studies in patients with T2DM have shown that DPP-4 inhibitors reduce elevated A1C, lower postprandial and fasting glucose, suppress glucagon release, and are weight neutral. Collectively, these new drugs, given in combination with other antidiabetic agents, such as metformin, sulfonylureas, and/or thiazolidinediones, can help restore glucose homeostasis in poorly controlled patients with T2DM.
Davidson
Jaime A
JA
Department of Medicine, Division of Endocrinology, University of Texas Southwestern Medical School, Dallas, TX 75230, USA. davidsonmd@sbcglobal.net
Parente
Erika B
EB
Gross
Jorge L
JL
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D000077270:Exenatide; D005215:Fasting; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D019518:Postprandial Period; D011719:Pyrazines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use; D000077597:Vildagliptin
D000218:Adamantane; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D009570:Nitriles; D010455:Peptides; D011719:Pyrazines; D011759:Pyrrolidines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D014688:Venoms; D000077597:Vildagliptin