Oral Insulin: A Comparison With Subcutaneous Regular Human Insulin in Patients With Type 2 Diabetes

OBJECTIVE: To determine the pharmacokinetic and pharmacodynamic properties of an oral insulin (OI) formulation compared with subcutaneously injected regular human insulin (RHI). RESEARCH DESIGN AND METHODS: Ten male patients with type 2 diabetes (means ± SD; A1C 7.0 ± 1.1%; BMI 28.3 ± 2.7 kg/m(2)) received either 300 units of insulin combined with 400 mg of delivery agent orally or 15 units RHI subcutaneously under isoglycemic clamp conditions. RESULTS: Maximum insulin concentration was greater and onset of action was faster with OI (C(max) 93 ± 71 vs. 33 ± 11 μU/ml; AUC(GIR)((0−1h)) 173 ± 86 vs. 27 ± 32 mg/kg; P < 0.05). Mean insulin concentration and glucose infusion rate returned to baseline within 3 h after OI administration. Relative bioavailability of OI was 7 ± 4% (1st 2 h). CONCLUSIONS: This proof-of-concept study demonstrated that absorption of OI is feasible under fasting conditions. OI has a fast onset and a short duration of action but also shows a rather high between-subject variability in absorption.