| Outcome Measures: |
Primary: Beta-cell Function After 52 Weeks of Therapy, Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period \[i.e., clamp time 290 min to 300 min\]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline \[week -2\])., Baseline (week -2) and 52 weeks | Secondary: Beta-cell Function 4 Weeks After Cessation of Therapy, Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period \[i.e., clamp time 290 min to 300 min\]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline \[week -2\])., Baseline (week -2) and 56 weeks|Change in First Phase C-peptide Release, Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline \[week -2\]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure., baseline (week -2), 52 weeks, and 56 weeks|Change in Second Phase C-peptide Release, Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline \[week -2\]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure., baseline (-2 weeks), 52 weeks, and 56 weeks|Change in Glycosylated Hemoglobin (HbA1c), Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0)., Week 0 and week 52|Change in Fasting Plasma Glucose, Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0)., 0 weeks and 52 weeks|Seven Point Self Monitored Blood Glucose (SMBG) Measurements, SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime)., 0 weeks and 52 weeks|Change in Body Weight, Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0)., 0 weeks and 52 weeks|M-value at Baseline, Week 52 and Week 56, M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp., baseline (week -2), 52 weeks, and 56 weeks
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