Lead investigator Dr Robert Heine (VU University Medical Center, Amsterdam, the Netherlands) presented the results of the study this week at the American Diabetes Association annual meeting and reported that "exenatide can be an effective alternative to starter basal insulin for type 2 diabetic patients suboptimally controlled with metformin and sulfonylurea therapy."

Exenatide is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster, a lizard native to the Southwest US. The drug is known as an incretin mimetic and exhibits many of the same effects as the human incretin hormone glucagonlike peptide 1 (GLP-1), such as stimulating insulin production, regulating the proliferation of insulin-producing islet cells in the pancreas, and slowing gastric emptying.


The primary objective of this 26-week study was to determine whether comparable glycemic control could be achieved in patients randomized to exenatide and insulin glargine, as measured by a change in hemoglobin A1_c (HbA1_c) levels. Patients were randomized to exenatide 5 µg twice a day for the first four weeks and 10 µg twice a day for the remainder of the study, while the insulin-treated patients received 10 insulin units per day. Both treatment groups were receiving background metformin and sulfonylurea therapy. Age, gender, body weight, BMI, and duration of diabetes were similar between both patient groups.

At the end of the study period, both patient groups achieved similar reductions in HbA1_c levels, with approximately half of the patients in both arms achieving the target HbA1_c level of less than 7%. There was a significant difference in weight loss between the two treatment arms. Patients in the exenatide study arm lost, on average, 2.3 kg whereas those treated with insulin glargine gained, on average, 1.8 kg. Exenatide also reduced postprandial blood glucose levels following breakfast and dinner, while insulin glargine was more effective at reducing fasting glucose levels. Hypoglycemia was also rare in both study groups, with rates similar in both treatment arms.

Heine reported that of the 283 patients randomized to exenatide, 55 patients (19.4%) withdrew from the study. Of these, 27 withdrew because of an adverse event. In contrast, 26 patients in the insulin glargine-study arm withdrew, just two because of adverse events.

"The most common adverse events with exenatide were GI-related, as would be expected," said Heine. "Nausea was reported in 57% of the exenatide-treated patients and 9% of the insulin-glargine-treated patients. Most of the nausea was mild to moderate and tended to decrease over time." Heine added that the weight reduction was not attributed to the nausea, as an analysis of those patients who experienced vomiting and/or nausea showed similar weight reductions compared with those who did not experience this adverse event.