| Outcome Measures: |
Primary: The safety and tolerability of repeat doses of HIP2B in subjects with type 2 diabetes mellitus., Safety evaluations will include clinical observation and adverse event (AE) reporting; evaluation of the injection site, physical examination, vital signs; electrocardiograms (ECGs), hematology, chemistry panels (inclusive of expanded markers of liver function), dipstick urinalysis (microscopic evaluation if dipstick positive), amylase, LDH., Adverse Events / vitals are monitored at each study visit between Days -9 and 84. | Secondary: Glucose-stimulated insulin secretion., First-phase insulin response will be assessed (a) as the incremental insulin peak (above baseline) after glucose injection during the IVGTT and (b) as the incremental insulin area obtained over 10 min; incremental area under the curve (AUC) during the GGI will be calculated for insulin and C-peptide., IVGTT performed on Day -8 and Day 49. GGI performed on Day -1, Day 25 and Day 46. | Other: Pre-hepatic insulin secretion rate., The pre-hepatic insulin secretion rate will be calculated based on deconvolution of peripheral C-peptide concentrations during GGI using the method described by Hovorka et al., GGI used for assessments is performed on Day -1, Day 25 and Day 46.|Change in β-cell responsiveness., Change in β-cell responsiveness will be assessed by comparing the slopes of the change of plasma insulin against glucose before and after treatment., GGI measured on Day-1, Day 25 and Day 46.|PK parameters of HIP2B after single and repetitive dosing., PK parameters of HIP2B: e.g. Cmax, Tmax, AUC (0.t), AUC(0-∞), CL/F, V/F, t½., PK testing done on Day 1 and Day 46 at pre-dose, 15 and 30min, 1 and 2 hours post dose.|Pharmacodynamic (PD) effects of repeat doses of HIP2B on measures of glycemic control and β-cell function, Pharmacodynamic (PD) effects of repeat doses of HIP2B on measures of glycemic control and β-cell function including fasting plasma glucose, fasting C-peptide, fasting proinsulin/insulin ratio and HOMA-B; glycated albumin, HbA1c, and 7-point glucose profiles., Assessments completed at screening, Days -9, -8, -2, -1, 1, 7, 14, 21, 24, 28, 42, 45, 46, 48, 49, 61, 68, and 84.
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