Exenatide - a physiological option for a pathological disease

Thursday, September 17, 2009

NEW DELHI - The treatment of Type 2 diabetic patients, especially those who are obese, is full of challenges.

According to Dr. Vikas Ahluwalia, President of the Diabetes Care Foundation of India, apart from blood sugar levels, there are several other treatment end points and issues that need to be addressed in such patients.

He says that the basic pathophysiology of type 2 diabetes includes three main defects, namely insulin deficiency, excess glucose output and insulin resistance.

Despite the advances in the management of diabetes and development of newer better insulins, there are various unsolved problems in the treatment of obese type 2 diabetic patients as in:

1. HbA1c targets are achieved only in a minority of patients.

2. Increase in body weight by most anti-diabetic drugs (insulin, sulfonylureas, glitazones)

3. Weight gain is associated with an increase in blood pressure, LDL, and chronic inflammation as well as decrease in HDL.

4. Risk of severe hypoglycemia is high in type 2 diabetic with long standing disease.

5. Continuous progression of diabetes deterioration caused by beta cell loss.

Recently increased evidence from multiple randomized control studies have shown that drugs mimicking the physiological incretin effect on insulin secretion provide better and effective blood sugar control in obese diabetics, Dr Ahluwalia says.

Incretin hormone secretion and actions are impaired in type 2 diabetes. Also beta cell responsiveness to GLP - 1 is reduiced, but exogenous GLP - 1 can still restore beta cell sensitivity to glucose and improve glucose induced insulin secretion.

One such drug called Exenatide (Byetta), which is a synthetic version of salivary protein found in the gila monster, binds to human GLP - 1 receptors on beta cells in vitro. Such incretin based therapies of type 2 diabetes may be expected to reduce hyperglycemia and HbA1c levels, improve alpha cell and beta cell function, improve insulin sensitivity and improve metabolism.

Exenatide is not beneficial for every type 2 duabetic patient. Patient selection is very important before starting exanatide. It is primarily indicated in the following situations:

1. BMI > 30

2. HbA1c > 8.5 on 2/3 antidiabetic drugs

3. not willing for SMBG

4. always feels hungary

5. wants to lose weight

6. anxious about hypoglycemia with insulin.

As with insulin, Exenatide has to be injected subcutaneously once or twice daily. Main side effects include nausea, diarrhea and pancreatitis (0.3 cases in 1000 patients). By Dr. Vikas Ahluwalia(ANI)

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