Oral insulin: a comparison with subcutaneous regular human insulin in patients with type 2 diabetes

Abstract

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 microU/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.

Trial registration: ClinicalTrials.gov NCT00982254.

Figure 1

A: Pharmacokinetic (plasma insulin concentration) response to administration of an oral insulin formulation (uninterrupted line) and subcutaneous regular human insulin (dotted line) at time = 0 h. Plasma insulin concentrations are presented as means ± SEM. AUC_INS^(0−1h): 2,559 ± 1,831 vs. 542 ± 296 μU · min⁻¹ · ml⁻¹, P < 0.05, AUC_INS^(0−6h): 3,225 ± 2,320 vs. 7,004 ± 2,440 μU · min⁻¹ · ml⁻¹, P < 0.05. B: Pharmacodynamic (GIR) response. GIRs are given for mean raw (thin line) and smoothed (bold line) data. AUC_GIR^(0−1h): 173 ± 86 vs. 27 ± 32 mg/kg, P < 0.05. AUC_GIR^(0−2h): 297 ± 143 vs. 137 ± 107 mg/kg, P < 0.05. AUC_GIR^(0−6h): (374 ± 135 vs. 651 ± 380 mg/kg). T_GIRmax: 40 ± 16 vs. 255 ± 108 min, P < 0.05. T_{GIR-50%-early}: 13 ± 6 vs. 150 ± 87 min, P < 0.05. T_GIR-50%-late: 115 ± 79 vs. >360 min, P < 0.05. GIR_max: 4.4 ± 2.2 vs. 3.6 ± 1.8 mg · kg⁻¹ · min⁻¹. sc, subcutaneous.