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Exenatide Delivers Weight-Reduction Benefit in Type 2 Diabetes

Patients with type 2 diabetes who take the new incretin mimetic drug exenatide (Byetta) appear to achieve sustained glucose control and progressive weight reduction after 18 months of therapy. In the study of patients who had failed to achieve adequate control with standard therapy, the switch to injectible exenatide also appeared to improve lipid profiles and reduce blood pressure.

"These findings — the first long-term data we have had on this drug — demonstrate that it may be especially beneficial for patients who have been unsuccessful in achieving effective management," said study coinvestigator David Kendall, MD, chief of clinical services and medical director of the International Diabetes Center in Minneapolis, Minnesota. "We did not see any new safety issues with longer term use — the GI [gastrointestinal] effects were consistent with what we saw in the earlier trials."
At baseline, participants’ mean age was 56 years, mean body mass index was 34 kg/m2, and the times since diagnosis of type 2 diabetes was seven years. Patients who received the 10-µg dose in combination with metformin and/or a sulfonylurea, attained an A1C reduction of 1.2% from baseline and lost an average of 12.1 lb for the study period. A total of 83% of participants lost weight for the duration of the study period.

The incretin mimetics work by mimicking the glucose-lowering actions performed by human incretin hormones. In diabetes, the drug works to stimulate insulin production and inhibit postprandial release of glucagon.

The study involved 146 patients who remained in an extension of a trial that originally included 285 patients and who completed 82 weeks of treatment. The most common adverse effect was nausea, which affected less than 10% of patients in the extension study, and appeared to decrease over time in most affected patients, Dr. Kendall noted. He also cautioned that patients who take sulfonylureas in conjunction with exenatide may experience periodic hypoglycemia, possibly necessitating a reduction in the sulfonylurea dose. In addition, the drug is contraindicated for individuals with severe renal disease.

Joseph Prendergast, MD, an endocrinologist in Redwood City, California, who recently began treating patients with exenatide, thinks that the drug itself and the development of incretins, represent a milestone in endocrinology. "This is a major development and it is potentially advantageous for those patients who have not been successful with standard approaches," Dr. Prendergast said. "This really is the most exciting time in the history of the field [endocrinology], and the concept of multiple-target [drugs] also appears intriguing and promising."

Presented at the American Diabetes Association’s 65th Annual Scientific Sessions.

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