Pharmacokinetic and Pharmacodynamic Variability of Insulin When Administered by Jet Injection

Abstract

Background:Jet injection has been shown to accelerate the absorption and action of rapid-acting insulin. In this study, we compared the variability of absorption characteristics between jet injection and conventional administration of the rapid-acting insulin analogue aspart.Methods:A total of 30 healthy volunteers were enrolled in this randomized controlled blinded parallel study. On two test days, they received insulin aspart (0.2 units/kg body weight), either by jet injection or conventional pen, followed by a 6-hour euglycemic glucose clamp. Plasma glucose and insulin levels and glucose infusion rates were measured every 5 to 10 minutes to calculate the variability in pharmacological endpoints.Results:Jet injection advanced the times until maximal insulin concentration (T-INSmax) and glucose infusion rate (T-GIRmax) by ~40% (both P < .01). The difference between the two test days for these endpoints did not differ between jet injection and conventional administration (T-INSmax: 7.3 ± 1.9 vs 22.3 ± 6.3 min, P = .074; T-GIRmax: 24.0 ± 3.5 vs 27.3 ± 6.6 min, P = .66). The corresponding intraindividual coefficients of variation for injection by jet or conventional pen were 15.3 ± 3.3 and 22.0 ± 4.6% (P = .25, Pvariance = .044) for T-INSmax and 34.5 ± 5.1 and 21.2 ± 4.6% for T-GIRmax (P = .064, Pvariance = .62). The variance in maximal insulin concentration was significantly less after conventional administration (P = .039). The variance in total glucose-lowering effect and total insulin exposure did not differ (P = .93 and P = .32)Conclusion:Using a jet injector for insulin administration was associated with slightly altered variability in pharmacokinetic endpoints, but with about similar variability in pharmacodynamic endpoints compared to conventional administration. Variability in these endpoints remains considerable, regardless of the method of insulin administration.

Factors Affecting the Absorption of Subcutaneously Administered Insulin: Effect on Variability

“…Use of jet injection, where insulin is administered at high velocity across the skin, instead of conventional pen administration has been shown to accelerate absorption of insulin aspart in healthy subjects and persons with diabetes [ 162 , 163 ]. The jet injection results in the depot being dispersed in a spray-like manner in the SC tissue, thus increasing the surface-to-volume ratio of the injection depot that is likely the mechanism behind the accelerated absorption [ 163 ].…”

“…The jet injection results in the depot being dispersed in a spray-like manner in the SC tissue, thus increasing the surface-to-volume ratio of the injection depot that is likely the mechanism behind the accelerated absorption [ 163 ]. Elsemiek et al observed a 40% shorter T max and a significantly higher C max with jet compared to pen administration in healthy subjects [ 162 ]. Moreover, use of jet injection has also been reported to be beneficial in terms of diminishing the obesity-associated delay in insulin absorption compared to pen injections [ 129 , 164 ].…”

Insulin delivery with a needle-free insulin injector versus a conventional insulin pen in Chinese patients with type 2 diabetes mellitus: A 16-week, multicenter, randomized clinical trial (the FREE study)

“…A run-in period from week 1 to the end of week 4 was implemented to allow treatment adjustment. Since regular insulin (RI) injected through a needle-free injector has shown a similar pharmacological profile to rapid-acting insulin [9,10], we reduced the insulin dosage when switching the insulin injecting device from a CIP to the NFII to avoid transient hyperinsulinemia, as this may lead to hypoglycemia. In patients previously using premixed insulin, those assigned to the NFII group had their insulin dosage reduced by 10%.…”

“…Needle-free injections of insulin have considerably enhanced insulin absorption and the consequent glucose-lowering effect, as well as achieving faster correction of hyperglycemia in short-term and small-scale trials in healthy volunteers and patients with diabetes [9,10]. However, whether these benefits can translate to better or equivalent glycemic control compared with needle-based insulin injections and improve patient satisfaction with treatment needs to be tested in larger and longer-term trials, since insulin treatment is a long-term therapy administered by patients themselves in ambulatory settings under the supervision of clinicians.…”

ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes

“…The benefits of these devices are that the needle is hidden from view and the needle is inserted through the skin rapidly. Automatic injection devices for specific insulin injectors are available …”