Can Incretin Mimetics Improve Beta Cell Dysfunction

By Mackenzi Nelson, DPM, and John S. Steinberg, DPM

      This is a fascinating finding because salivary glands do not have known endocrine function in vertebrates and proteins generally have a decreased ability to cross cell membranes.10 Further studies are warranted to evaluate the mechanism by which exendin-4 is released into the bloodstream.

Pertinent Pearls On Using Byetta

      One would administer exenatide twice daily before meals as a subcutaneous injection, delivering doses of 5 mcg or 10 mcg.4,8,12 The use of the medication is contraindicated in patients with type 1 diabetes and for diabetic ketoacidosis treatment. The use of Byetta in patients with end-stage renal disease or severe renal insufficiency is not recommended due to a high reduction of clearance. However, a mild disease state does not limit use.8

      The greatest adverse effect noted in all studies was gastrointestinal in nature, with nausea noted predominately. Although nausea was most commonly reported, researchers noted it was primarily limited to a few weeks after initiation of treatment.3,5,8,12 Due to the gastrointestinal nature of the side effects, the use of Byetta in patients with gastrointestinal disorders is also not recommended. In addition, Byetta may cause skeletal effects in fetuses and consequently should only be used in pregnancy if the benefit outweighs the risk.8

      Hypoglycemia is of major concern with all anti-diabetic agents. While the combination of Byetta with metformin produced no increase in hypoglycemia, using Byetta with a sulfonylurea has shown an increased risk of hypoglycemia.3,5,6,8 This risk is highly dose-dependent. When using Byetta, one should lower the sulfonylurea to limit the incidence of hypoglycemia.

In Conclusion

      There is a great deal of ongoing research into new pharmacologic agents for diabetes. Ongoing research includes incretin enhancers as the next possible class of oral agents. Exenatide injection therapy has proven to be an effective adjunctive drug therapy for patients with uncontrolled diabetes. This therapy not only works to improve blood sugars but also helps improve beta cell function and beta cell mass. Indeed, this combination of benefits is unlike what one would obtain with most other blood glucose lowering agents. With the advent and use of Byetta, it seems that this drug can delay or even prevent the progression of the disease.

      Dr. Nelson is a second-year podiatric resident at Washington Hospital Center in Washington, DC.

      Dr. Steinberg (pictured) is an Associate Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C.

      Editor’s note: For related articles, see “Is Inhaled Insulin A Viable Alternative For Patients With Diabetes?” in the October 2006 issue of Podiatry Today.

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