Incretin hormone mimetics and analogues in diabetes therapeutics.
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are physiological gut peptides with insulin-releasing and extrapancreatic glucoregulatory actions. Incretin analogues/mimetics activate GLP-1 or GIP receptors whilst avoiding physiological inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the newest classes of antidiabetic drug. The first clinically approved GLP-1 mimetic for the treatment of type-2 diabetes is exenatide (Byetta/exendin) which is administered subcutaneously twice daily. Clinical trials of liraglutide, a GLP-1 analogue suitable for once-daily administration, are ongoing. A number of other incretin molecules are at earlier stages of development. This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. Additionally, it explores the therapeutic possibilities offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon hybrid peptides, and specific GIP receptor antagonists.
Green
Brian D
BD
School of Biological Sciences, Queens University Belfast, David Keir Building, Stranmillis Road, Belfast BT6 0NJ, Northern Ireland, UK. b.green@qub.ac.uk
Flatt
Peter R
PR
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D000077270:Exenatide; D005749:Gastric Inhibitory Polypeptide / Q000819:agonists / Q000737:chemistry / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000819:agonists / Q000031:analogs & derivatives / Q000737:chemistry / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D000069450:Liraglutide; D008969:Molecular Sequence Data; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors; D014688:Venoms
D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D014688:Venoms; D005749:Gastric Inhibitory Polypeptide; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C041086:gastric inhibitory polypeptide receptor; D018819:Dipeptidyl Peptidase 4