Management of Type 2 diabetes is becoming more aggressive in terms of targets for treatment. It is also becoming more complex, as new classes of agents for the treatment of this condition have recently become available. This article focuses on a new treatment, Incretin Therapy.

Incretins are big news in the management of Type 2 diabetes. They are naturally occurring hormones secreted by the small intestine and in recent times their role in the pathophysiology of Type 2 diabetes has gained prominence. The incretin therapies are now emerging as important new treatments in the management of Type 2 diabetes. There are currently many new agents around the world in development or available for clinical use. These include the incretin mimetics which are resistant to degradation, and DDP 4 inhibitors which reduce the degradation of naturally occurring incretin hormones.

Incretins are secreted in response to an oral glucose load and these agents act directly on the pancreas beta cell to enhance insulin secretion. They also act on the pancreatic alpha cell causing inhibition of glucagons secretion. In addition to this, there are extra pancreatic effects that benefit carbohydrate metabolism and glycaemic control. GLP-1 slows gastric empyting and increases satiety. These important effects reduce post prandial blood glucose rises as well as appetite and food intake. In Type 2 diabetes GLP-1 levels are significantly reduced and incretin responses to oral glucose are known to be impaired. Within minutes of secretion the incretins are rapidly degraded by the enzyme DPP 4. GLP-1 analogues have therefore been developed which are resistant to DPP 4 degradation. Similarly DPP 4 inhibitors are now available to enhance the body’s naturally occurring levels of incretins.

There have been many clinical studies showing the benefits of incretin hormone therapy. A number of GLP-1 analogues have been developed and the first of these to be used in clinical practice is exanatide. Exanatide (Byetta) is a twice daily GLP-1 analogue administered by sub-cutaneous injection. Studies have shown benefits in improving glycaemic control in associating with significant weight loss. This is in contrast to most agents available today for the clinical treatment of Type 2 diabetes which improves glycaemic control in association with weight gain. Byetta is currently available on private prescription in Australia at present and the cost is approximately $200 per month. It is suitable for use in patients on oral hypoglycaemic agents with inadequate diabetic control. It has also been used in some patient groups as an addition to insulin therapy. The main side effects are nausea and vomiting and in about 30% of patients this agent is not tolerated. There are many other GLP-1 analogues currently under development. A long acting exanatide injection which is once weekly is currently undergoing trials and other groups are working on once daily GLP-1 analogues.

The first of the DPP4 inhibitors is sitagliptin (Januvia). Januvia is a new oral agent available for use in Type 2 diabetes. Currently in Australia this is available on the PBS but is restricted for use in dual therapy with either a sulphonylurea or metformin where dual therapy with both of these agents is not tolerated or is contra indicated. For patients who do not fulfil the PBS criteria, cost on private prescription is approximately $100 per month. This agent improves glycaemic control without weight gain but unlike the GLP-1 analogues it is weight neutral. The side effect profile is extremely low and mainly consists of skin rash, itching and allergic type response. One of the great advantages of this agent over the sulphonylurea group is the lack of hypoglycaemia. Insulin responses to incretin therapy are all glucose dependent and therefore it does not carry the same risk of hypoglycaemia. These are many DDP 4 inhibitors currently undergoing clinical trials. They are emerging as important oral agents for the treatment of Type 2 diabetes.

Dr. Neale Cohen is an Endocrinologist and General Manager of Diabetes Services, Baker IDI. Baker IDI Heart and Diabetes Institute is the nation’s premier health and medical research institute tackling the deadly trio of obesity, diabetes and cardiovascular disease. Baker IDI research extends from the laboratory to wide-scale community studies along with the leading education forum for health professionals in the area of diabetes and disease management. For further information, please visit www.bakeridi.edu.au

Tags: diabetes