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EXENATIDE

Exenatide (also Exendin-4, marketed as Byetta) is the first of a new class of medications approved for the treatment of Type 2 diabetes. It is an incretin mimetic, which has glucoregulatory effects. It is to be used in conjunction with oral medications such as metformin and/or a sulfonylurea to improve glucose control. The medication is injected twice per day using a specially designed pen. The typical human response is both an improvement of the release of internal insulin by the pancreas and suppression of pancreas glucagon release, behaviors more typical of individuals without blood sugar control problems. In the presence of exenatide, these responses are greater when the blood sugar is elevated.

Contents

Development History

The incretins hormones GLP-1 (glucagon-like peptide-1) and GIP are produced by the endocrine cells of the intestine following ingestion of food. GLP-1 and GIP stimulate insulin secretion from the beta cells of the islets of Langerhans in the pancreas. Only GLP-1 causes insulin secretion in the diabetic state, however GIP is ineffective. GLP-1 itself is ineffective as a clinical treatment for diabetes as it has a very short half-life in vivo. Exenatide bears a 50% amino acid homology to GLP-1 and thus was tested for it ability to stimulate insulin secretion and lower blood glucose in mammals and was found to be effective in the diabetic state. It has a longer half-life in vivo. In studies on rodents it has also been shown to increase the number of beta cells in the pancreas.

Commercially, exenatide is produced by direct chemical synthesis. Given the history of the drug, and though it is -- strictly speaking -- not so, it is sometimes referred to as "lizard spit".

It was approved by the FDA as an adjunctive therapy for use with metformin, in the US in April 2005 and is currently marketed as Byetta.

Mode of action

Exenatide works to help improve glucose control in at least four ways:

  • Exenatide augments pancreas response to release a higher, more appropriate amount of insulin in response to eating meals; this helps lower the rise in blood sugar rise from eating to more normal, flatter response levels. If blood sugar levels get closer to normal, the pancreas response to produce insulin is reduced. Other drugs (like injectable insulin itself) are effective at lowering blood sugar, but can "overshoot" their target and cause blood sugar to become too low, resulting in the dangerous condition of hypoglycemia.
  • Exenatide also suppresses pancreas release of glucagon in response to eating, which helps stop the liver from overproducing sugar when it is unneeded, which prevents hyperglycemia (high blood sugar levels).
  • Exenatide helps slow down gastric emptying (the rate at which sugar enters the bloodstream) which also helps avoid hyperglycemia.
  • Exenatide has a subtle yet prolonged effect to reduce appetite, overeating and weight gain. Most people using Exenatide slowly lose weight. Though mild, clinical trials have demonstated that the weight reducing effect continues at the same rate through 2.25 years of continued use.

While other treatment options share one or more of the first three characteristics, many diabetics specialists view exenatide as a significant improvement over other available diabetic medications. In addition to its strong safety profile, the improved weight control is important for diabetes treatment; except for metformin, all other available drugs for improving glucose control have been associated with weight gain.

Long-acting-release formulation

Eli Lilly & Co., Amylin Pharmaceuticals and Alkermes, Inc. are currently developing a long-acting-release (LAR) formula of the drug, which would be injected once per week. The initial trials for the medication have shown the LAR formulation to be as effective as the original twice-daily injectible form, with a similar safety and weight loss profile.

External links

Pills  This pharmacology-related article is a stub. You can help Wikipedia by expanding it. 
NEW YORK, June 26 (Reuters) - Nastech Pharmaceutical Co. Inc. (NSTK.O: Quote, Profile, Research) said on Monday it had reached an agreement with Amylin Pharmaceuticals, Inc. (AMLN.O: Quote, Profile, Research) to develop a nasal spray formulation of exenatide, a treatment for type 2 diabetes.

Nastech would receive milestone payments of up to $89 million and royalties on product sales if development were successful and the program moved forward.