Body mass index and the efficacy of needle-free jet injection for the administration of rapid-acting insulin analogs, a post hoc analysis.

We recently showed in a euglycaemic glucose clamp study among 18 healthy volunteers that using jet injectors rather than conventional pens significantly improved the time-action profiles of rapid-acting insulin analogs. Here, we investigated whether such profiles were modified by body mass index (BMI) and related weight parameters by comparing insulin administration by jet injection to that by conventional pen in subgroups defined by BMI, waist-to-hip ratio, waist circumference and insulin dose. After conventional administration, times to peak insulin levels (T-INS(max)) occurred 31.1 [95% confidence interval (CI) 13.7-48.5] min later and time to maximum glucose requirement (T-GIR(max)) 56.9 (95%CI 26.6-87.3) min later in more obese (BMI > 23.6 kg/m(2)) than in lean subjects (BMI < 23.6 kg/m(2)). In contrast, T-INS(max) and T-GIR(max) were similar in subjects with high and low BMI, when insulin was administered by jet injection. We conclude that using jet injection for insulin administration may especially benefit subjects with higher body weight.

Decreased active GLP-1 response following large test meal in patients with type 1 diabetes using bolus insulin analogues.

Postprandial plasma immunoreactive active glucagon-like peptide-1 (p-active GLP-1) levels in type 1 diabetic patients who did not use bolus insulin responded normally following ingestion of test meal, while a small response of p-active GLP-1 levels was seen in type 2 diabetic patients. To determine whether p-active GLP-1 levels are affected by ingestion of test meal in type 1 diabetic Japanese patients who used bolus rapid-acting insulin analogues, plasma glucose (PG), serum immunoreactive insulin (s-IRI), serum immunoreactive C-peptide (s-CPR), and p-active GLP-1 levels were measured 0, 30, and 60 min after ingestion of test meal in Japanese patients without diabetic complications (n=10, group 1) and control subjects with normal glucose tolerance (n=15, group 2). HbA1c levels were also measured in these groups. The patients in group 1 were treated with multiple daily injections or CSII using injections of bolus rapid-acting insulin analogues before ingestion of test meal. There was no significant difference in mean of sex, age, or BMI between groups. Means of HbA1c, basal and postprandial PG, and postprandial s-IRI levels with integrated areas under curves (0-60 min) (AUC) in group 1 were significantly higher than those in group 2. Means of basal and postprandial s-CPR, and postprandial p-active GLP-1 levels with AUCs were significantly lower in group 1 than in group 2. These results indicated that postprandial p-active GLP-1 levels following ingestion of test meal in type 1 diabetic Japanese patients using bolus rapid-acting insulin analogues were decreased relative to those in controls.

Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology.

OBJECTIVE: Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe, which may facilitate a more rapid absorption. This study compared the pharmacologic profile of administration of insulin aspart by jet injection to that by conventional insulin pen. RESEARCH DESIGN AND METHODS: Euglycemic glucose clamp tests were performed in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body wt of aspart, either administered by jet injection or by conventional pen, using a randomized, double-blind, double-dummy, cross over study design. Pharmacodynamic and pharmacokinetic profiles were derived from the glucose infusion rate (GIR) needed to maintain euglycemia and from plasma insulin levels, respectively. RESULTS: The time to maximal GIR was significantly shorter when insulin was injected with the jet injector compared with conventional pen administration (51 ± 3 vs. 105 ± 11 min, P < 0.0001). The time to peak insulin concentration was similarly reduced (31 ± 3 vs. 64 ± 6 min, P < 0.0001) and peak insulin concentrations were increased (108 ± 13 vs. 79 ± 7 mU/L, P = 0.01) when insulin was injected by jet injection compared with conventional pen injection. Jet injector insulin administration reduced the time to 50% glucose disposal by ∼40 min (P < 0.0001). There were no differences in maximal GIR, total insulin absorption, or total insulin action between the two devices. CONCLUSIONS: Administration of insulin aspart by jet injection enhances insulin absorption and reduces the duration of glucose-lowering action. This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postprandial glucose excursions.