Intradermal insulin infusion achieves faster insulin action than subcutaneous infusion for 3-day wear

Abstract

Rapid uptake previously demonstrated by intradermal (ID) drug administration indicates compound delivery within the dermis may have clinical and pharmacological advantages for certain drug therapies. This study is the first clinical trial to evaluate continuous microneedle-based drug infusion, device wearability, and intradermal microneedle insulin kinetics over a multi-day (72 h) wear period. This was a single center, open-label, two-period crossover study in T1DM patients on continuous subcutaneous insulin infusion (CSII). Patients received treatment during interventional visits: one SC and one ID basal/bolus infusion of insulin aspart (NovoRapid® U-100) administered over 3 days in a randomized order. Twenty-eight patients were randomized and exposed to trial product, and 23 completed the study. Bolus insulin infusions were given prior to standardized breakfast and lunch test meals on each of the three treatment days. Blood samples were drawn at predefined time points for measurements of insulin aspart and blood glucose in serum. The primary endpoint insulin Tmax demonstrated that ID bolus infusion was associated with a significantly shorter Tmax with statistically significantly smaller intra-subject variability, compared to SC infusion, and this difference was maintained over three treatment days. Analyses of secondary PK endpoints corresponded with the primary endpoint findings. Postprandial glycemic response was significantly less pronounced after ID bolus: For most endpoints ID vs. SC, differences were statistically significant within the 0–1.5 or 0–2 h time period. Intradermal delivery of insulin is a viable delivery route alternative providing reduced time for insulin absorption with less intra-subject variability and lower glycemic response.

Improved Insulin Pharmacokinetics Using a Novel Microneedle Device for Intradermal Delivery in Patients with Type 2 Diabetes

“… 20 ID delivery of insulin demonstrated safety and efficacy in continuous infusion through a microneedle-based continuous insulin infusion pump. 21 …”

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

“…Although the dermal route may actually offer a more rapid absorption of insulin compared to the SC route, dermal injections have traditionally been more difficult to perform and may result in increased immune response activation, injection pain, and insulin leakage [ 28 ]. Microneedles may overcome some of these issues, although patients may experience more pain due to a high delivery pressure as a result of increased tissue density and decreased needle diameter [ 29 – 31 ], making this route less suitable for injection of larger volumes.…”

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

“…Absent or reduced levels of insulin (underlying type 1 and overt 2 diabetes, respectively) can profoundly compromise the anabolic action of the hormone, exemplified by glucose disposal in muscle and adipose tissues. Consequently, all type 1 diabetic and many type 2 diabetic individuals rely on subcutaneously injected insulin for survival and proper metabolic control (36). Typical injections of a short-acting insulin (formulated as 100 IU/ ml, which is equivalent to 600 M; Ref.…”