West Suffolk Diabetes Service


Drugs and New Products

 

FUTURE PRODUCTS

Exenatide (synthetic exendin-4)

What is Exenatide?

Exenatide, also known as synthetic exendin-4, is a new agent for the treatment of type 2 diabetes. Clinical trials suggest that exenatide treatment decreases blood glucose toward target levels and is associated with weight loss.

How does it work?

The effects on glucose control seen with exenatide treatment are thought to be due to several properties that are similar to those of the naturally occurring incretin hormone GLP-1. These actions include stimulating the insulin response in response to glucose and preventing glucagon (a hormone which raises blood sugar) release after meals.

Animal studies have shown that exenatide helped preserve and form new beta cells, the insulin-producing cells in the pancreas, which fail as type 2 diabetes progresses.

Tell me more…

Exendin-4, is a peptide made up of 39 amino acids. It is a powerful stimulator of a receptor known as GLP-1 (Glucagon Like Peptide – 1).

Exendin-4, therefore has similar properties to GLP-1. It is also more potent than GLP-1. It regulates gastric emptying, insulin secretion, food intake, and glucagon secretion.

I’ve heard this has something to do with lizards!

Yes, exendin-4 was initially isolated from the venom found in the saliva of a poisonous  lizard found in North America, known as the Gila monster. This lizard eats four times a year. When it eats, exendin-4 secreted in the saliva causes it’s pancreas to ‘switch on’.

Why is exendin-4 so effective?

Unlike most other oral hypoglycaemic drugs which work by a single mechanism, exendin-4 works by several mechanisms: it stimulates insulin secretion, slows emptying of the stomach and inhibits production of glucose by the liver. It also appears to suppress appetite and helps weight loss. This would be a particular advantage with type 2 diabetes.

Is there a ‘downside’?

The main drawback is that it has to be injected.

What evidence is available?

Early studies in small numbers of people with type 2 diabetes has shown that taking this drug results in lower blood sugar levels after meals. It was also found to reduce triglyceride concentrations after meals.

Is this another oral hypoglycaemic agent?

No it’s not. Exenatide is a peptide similar to insulin. It will be available in an injectable pen/cartridge delivery system, similar to those used for insulin.

Are there any side effects?

In these clinical trials, exenatide was well tolerated. Most of the reported side effects were mild or moderate. Nausea was the most common reported effect.

Who would use it?

People with type 2 diabetes who are not well controlled on diet and oral agents i.e. those not achieving target HbA1c levels on sulphonylureas, metformin or thiazolidenediones.

What preparations are being trialled?

Exenatide – given subcutaneously twice a day at breakfast and dinner.

Exenatide LAR (Long Acting Release). Work is currently underway to develop this preparation which may allow once-a-week to once-a-month administration of exenatide for the treatment of type 2 diabetes.

At what stage of development is this drug?

Exenatide is currently in Phase 3 clinical trials and it is anticipated the companies responsible will make application for licensing in 2004. It is not available for routine clinical use at present.

Can GLP-1R agonists like exendin-4 prevent the development of diabetes?

This is an exciting prospect which is currently being studied in animals.

 

Dr Nishan Wijenaike
Consultant Diabetologist
West Suffolk Diabetes Service

November 2003

 

Source: www.DiabeteSuffolk.com

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Bury St Edmunds, Suffolk IP33 2QZ, tel:01284 713000