• Thomas J Moretto, Denái R Milton, Terry D Ridge, Leigh A Macconell, Ted Okerson, Anne M Wolka, and Robert G Brodows.
• American Health Network, Indianapolis, Indiana, USA.
• Clin Ther. 2008 Aug 1;30(8):1448-60.

BackgroundEvaluation of exenatide monotherapy in patients with type 2 diabetes may be of clinical interest based on improvements in glycemic control and weight that have been reported with the use of exenatide in combination with oral antidiabetic agents.ObjectiveThe aim of this study was to evaluate the efficacy and tolerability of exenatide monotherapy in patients with type 2 diabetes naive to antidiabetic agents and whose disease was inadequately controlled with diet and exercise alone.MethodsThis 24-week, double-blind, placebo-controlled, parallel-group study was conducted at 23 centers across the United States, Puerto Rico, Romania, Russia, and India. Patients aged >or=18 years with type 2 diabetes were randomly assigned to receive exenatide 5 microg, exenatide 10 microg, or placebo administered SC BID. Patients were instructed by investigators to maintain their individualized prestudy diet and exercise regimens throughout the study. Efficacy measures included: glycosylated hemoglobin (HbA(1c)); fasting serum glucose (FSG); 6-point self-monitored blood glucose; percentages of patients achieving HbA(1c) values ResultsA total of 232 patients were included in the intent-to-treat population (130 men, 102 women; 68% white; mean [SD] age, 54 [10] years; duration of type 2 diabetes, 2 [3] years; weight, 86 [16] kg; body mass index, 31 [5] kg/m(2); HbA(1c), 7.8% [0.9%]). At end point, least-squares mean (SE) HbA(1c) reductions (%) from baseline were significantly greater with exenatide 5 and 10 microg than placebo (-0.7 [0.1] and -0.9 [0.1] vs -0.2 [0.1]; P = 0.003 and P < 0.001, respectively), as were FSG reductions (mg/dL) (-17.5 [4.0] and -18.7 [4.0] vs -5.2 [4.0]; P = 0.029 and P = 0.016, respectively). Changes in daily mean postprandial glucose excursions (mg/dL) from baseline to end point were significantly greater with exenatide 5 and 10 microg than placebo (-21.3 [2.7] and -24.7 [2.7] vs -8.3 [2.5]; both, P < 0.001). With exenatide 5 and 10 microg, 31% and 35% of patients achieved HbA(1c) or=1 treatment-emergent adverse event. Nausea was reported with the greatest incidence (5 microg, 3%; 10 microg, 13%; placebo, 0%; P = 0.010 for the combined exenatide group vs placebo). Most (88%) treatment-emergent adverse events were mild or moderate in intensity. Hypoglycemia was reported in 5%, 4%, and 1% of patients in the exenatide 5- and 10-microg and placebo groups, respectively (P = NS), with no incidents of severe hypoglycemia reported.ConclusionsIn these patients with type 2 diabetes naive to treatment with antidiabetic agents, exenatide monotherapy was associated with improved HbA(1c), improved fasting and postprandial glucose control, reduced weight, improved beta-cell function (HOMA-B), and improved blood pressure, and was well tolerated. These results suggest that exenatide monotherapy may provide a viable treatment option beyond diet and exercise and support further study of exenatide monotherapy in antidiabetic drug-naive patients with type 2 diabetes.

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