Glucagon-like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials.
OBJECTIVE
To discuss the virtues and shortcomings of the glucagon-like peptide-1 receptor agonists and the dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes.


RESULTS
The injectable glucagon-like peptide-1 receptor agonists exenatide significantly improves glycaemic control, with average reductions in haemoglobin A1c of about 1.0%, fasting plasma glucose of about 1.4 mmol/l, and causes a weight loss of approximately 2-3 kg after 30 weeks of treatment in patients with type 2 diabetes. The adverse effects are transient nausea and vomiting. The long-acting glucagon-like peptide-1 receptor agonists liraglutide and exenatide long-acting release reduce haemoglobin A1c by about 1.0-2.0% and have fewer gastrointestinal side-effects. The orally available dipeptidyl peptidase-4 inhibitors, that is sitagliptin and vildagliptin reduce haemoglobin A1c by 0.5-1.0%, are weight neutral and without gastrointestinal side-effects.


CONCLUSIONS
The benefits and position of the glucagon-like peptide-1 analogues and the dipeptidyl peptidase-4 inhibitors in the diabetes treatment algorithm will be clarified when we have long-term trials with hard cardiovascular endpoints and data illustrating the effects on the progression of type 2 diabetes.
Department of Endocrinology, Hvidovre University Hospital, Hvidovre and University of Copenhagen, Copenhagen N, Denmark. sten.madsbad@hva.regionh.dk
Sten
S
Madsbad
Thure
T
Krarup
Carolyn F
CF
Deacon
Jens J
JJ
Holst
D000218:Adamantane / Q000031:analogs & derivatives; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide; D009570:Nitriles; D010455:Peptides; D011719:Pyrazines; D011759:Pyrrolidines; D018027:Receptors, Glucagon / Q000819:agonists*; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D014688:Venoms; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D009570:Nitriles; D010455:Peptides; D011719:Pyrazines; D011759:Pyrrolidines; D018027:Receptors, Glucagon; D014230:Triazoles; D014688:Venoms; D004763:Glucagon-Like Peptides; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate