Exenatide: a review from pharmacology to clinical practice.
BACKGROUND
Exenatide is an incretin mimetic that activates glucagon-like-peptide-1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose-dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying.


METHODS
In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c <or=11%), or by thiazolidinediones (with or without metformin) and treated for periods from 16 weeks to 3 years, exenatide (5 microg b.i.d. s.c. for the first 4 weeks of treatment and 10 microg b.i.d. s.c. thereafter) reduced HbA1c, fasting and postprandial glucose, and body weight dose dependently, and was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c. Body weight diminished with exenatide, whereas it increased with both insulin preparations. Positive effects on the lipid profile and a reduction in C-reactive protein were also recorded with exenatide. Treatment extensions up to 3 years showed that benefits were maintained in the long term. Adverse events were usually mild to moderate in intensity, and generally the frequency decreased with continued therapy. The most common was nausea (whose incidence may be reduced by gradual dose escalation from 5 microg b.i.d. to 10 microg b.i.d.), vomiting, diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated with a sulphonylurea).


CONCLUSIONS
Exenatide is a new, promising therapeutic option for type 2 diabetic patients inadequately controlled by oral agents, before insulin therapy, offering the added benefits of body weight reduction and tight postprandial glucose control.
Gentilella
R
R
Eli Lilly Italia, Sesto Fiorentino, Italy.
Bianchi
C
C
Rossi
A
A
Rotella
C M
CM
D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008297:Male; D010455:Peptides / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014688:Venoms / Q000627:therapeutic use*; D015431:Weight Loss
D001786:Blood Glucose; D002097:C-Reactive Protein; D000077270:Exenatide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D010455:Peptides; D014688:Venoms