Microneedle-Based Intradermal Versus Subcutaneous Administration of Regular Human Insulin or Insulin Lispro: Pharmacokinetics and Postprandial Glycemic Excursions in Patients with Type 1 Diabetes

Abstract

PPG with RHI administered ID via microneedle was improved versus SC delivery when dosed 17 min premeal. ID RHI provided similar control of PPG as SC IL immediately premeal. Further studies of ID insulin delivery via steel microneedles are warranted.

Pharmacokinetics and Postprandial Glycemic Excursions following Insulin Lispro Delivered by Intradermal Microneedle or Subcutaneous Infusion

“…In the two earlier studies with ID IL, Tmax was observed at ~58 and 64 min. 44,45 These differences with ID delivery remain potentially valuable for closedloop algorithm development. Another microneedle study has found similar acceleration of insulin PK.…”

Reduction of Postprandial Glycemic Excursions in Patients with Type 1 Diabetes: A Novel Human Insulin Formulation versus a Rapid-Acting Insulin Analog and Regular Human Insulin

“…[5][6][7] An ultra-fast insulin formulation has been developed [UFI; VIAject™ (Linjeta™), Biodel Inc., Danbury, CT]. Clinical experimental studies with healthy subjects have shown more rapid onset of absorption/action with UFI in comparison to insulin lispro (LIS) and RHI.…”

Insulin Therapy and Hypoglycemia - Present and Future

“…Delivery via microneedles resulted in faster insulin uptake with decreased time to maximal insulin concentration (by approximately 24 minutes), higher relative bioavailability at early post-injection times and a more physiologic metabolic effect, with faster onset of action (shorter times to maximal and early half-maximal glucose infusion rates) and more rapid offset of action (shorter time to late half-maximal glucose infusion rates) (90). Another clinical study was conducted in patients with type 1 diabetes in order to determine if the more rapid absorption of insulin resulting from microneedle administration translates into a significant reduction in postprandial glucose levels under standardized meal conditions (91). The results indicated that postprandial glucose levels were improved when regular human insulin was delivered intradermaly vs. subcutaneously, but were similar for analogue insulin.…”

“…The results indicated that postprandial glucose levels were improved when regular human insulin was delivered intradermaly vs. subcutaneously, but were similar for analogue insulin. In clinical studies the intradermal delivery was generally well tolerated (although some transient, localized wheal formation and redness were noticed at injection sites), but the potential effects of high level or repetitive exposure of protein drugs such as insulin on the lymphatics and immune system need full investigation (90,91). Another area of research focuses on the combination of available insulin products with a human recombinant hyaluronidase, which facilitates the local dispersion and absorption of co-administered molecules (92,93).…”