Pharmacology of exenatide (synthetic exendin-4) for the treatment of type 2 diabetes.
New therapies for the long-term treatment of type 2 diabetes are needed to ameliorate declining pancreatic beta-cell function. Ideally, these therapies should lower fasting and post-prandial blood glucose, produce no hypoglycemia or weight gain, cause no other limiting side effects, and reduce cardiovascular complications. Exenatide (synthetic exendin-4) is a potential therapeutic which may fulfill these criteria. Dose-ranging studies have identified an optimal dose of 0.05 to 0.2 microgram/kg administered subcutaneously twice daily. Pharmacokinetic data support a pivotal study design which mitigates the transient nausea observed in early studies by including a dose initiation period of 1 month at 5 micrograms twice daily, followed by maintenance therapy at 10 micrograms twice daily. Ongoing studies suggest exenatide improves glycemic control through a combination of mechanisms discussed in this review.
Nielsen
Loretta L
LL
Amylin Pharmaceuticals Inc., 9373 Towne Centre Drive, San Diego, CA 92121, USA.
Baron
Alain D
AD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014688:Venoms
D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D011994:Recombinant Proteins; D014688:Venoms