Diabetes Medications and New Drugs

Exenatide or Byetta (synthetic exendin-4)

Byetta Exenatide

What is Exenatide (Byetta)?

Exenatide or Byetta, also known as synthetic exendin-4, is a new agent for the treatment of type 2 diabetes. Research and clinical use confirms that Exenatide treatment lowers 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 (a protein) 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!

A Gila monsterYes, 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, it is thought that exendin-4 secreted in the saliva helps 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 is a particular advantage in people with type 2 diabetes who are also obese.

Is there a ‘downside’?

The main drawback is that it has to be injected. However, the needles used for injection are very fine and the injections are not considered to be ‘painful’.

At what stage of development is this drug?

Exenatide has been used widely in the United States over the past two years with good results. Exenatide is now available for use in the UK though prescribing on the NHS may be subject to local restrictions due to cost.

What evidence is available?

Studies in 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. The research has shown significant fall in HbA1c when Exenatide is added to existing therapy.

What is the effect of Exenatide on body weight?

Studies have shown that patients receiving Exenatide achieve weight loss in the region of 2.5kg, whereas those treated with insulin gain weight to a similar degree.

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.

Can Byetta be combined with other blood glucose lowering drugs?

Yes, it may be used in combination with Metformin or sulphonylureas. It is not licensed for combination with glitazones (Rosiglitazone or Pioglitazone) or insulin.

Are there any side effects?

The usual side effects are nausea vomiting and diarrhoea. Upto half of people starting on Exenatide will experience nausea, whereas between 10 – 15% will suffer from vomiting and/or diarrhoea. As treatment continues these symptoms do abate.

Patients taking sulphonylureas (eg. Gliclazide, Glipizide, Glimepiride) in addition to Exenatide, may suffer from hypoglycaemia.

Are there any dangerous side-effects?

The Food and Drug Administration of the USA has warned of a possible link of Exenatide with Pancreatitis which is a serious inflammation of the pancreas. This is based on reports of thirty patients who developed pancreatitis after starting on the drug. Twenty seven of these thirty patients had other risk factors for pancreatitis, however caution is advised.

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. It is particularly suitable in obese people as an alternative to insulin treatment.

What preparations are available?

Exenatide (Byetta) – 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 or even once-a-month administration of Exenatide for the treatment of type 2 diabetes. This is a very exciting prospect as it takes away the need for regular injections.

How is it administered and what is the dose?

Byetta is administered by subcutaneous injection. In this regard it is very similar to insulin therapy. As with most insulins, it is packaged in a pen injection device. The main difference when compared with insulin therapy is that you take a fixed dose of Byetta.

Byetta is available in either a 5mcg or 10 mcg dosage. Treatment is usually commenced at 5mcg twice daily for at least one month. This helps you get used to the drug and improves tolerability.

What time should I inject?

Byetta can be injected during the hour preceding your main meal in the morning and evening. It should not be injected after meals.

Advice on starting treatment with Byetta

When you start on Byetta it is usual to have symptoms of mild nausea. You may find that the problem diminishes with continued use. If you continue to have nausea do not increase to the full dose of 10mcg twice daily until the symptoms have settled down.

If you have been prescribed Exenatide in addition to a sulphonylurea (Gliclazide, Glipizide or Glimepiride) your doctor may consider reducing lowering the dose of sulphonylurea to help avoid hypoglycaemia.

If you take Warfarin, your INR should be closely monitored when Exenatide is commenced and during dose increases.

How much does it cost?

Byetta 10mcg twice daily for one month would cost in the region of 65. This appears expensive when compared with insulin therapy. However, in obese individuals who are insulin resistant, the large doses of insulin prescribed may outweigh the cost of Exenatide.

Is it available in Suffolk?

No. Exenatide cannot be prescribed in Suffolk until approved for use by the Suffolk Primary Care Trust.


Dr Nishan Wijenaike
Consultant Diabetologist
West Suffolk Diabetes Service
Updated October 2007


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