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

Background: This study assessed pharmacokinetics (PK) and pharmacodynamic postprandial glycemia (PPG) in patients with type 1 diabetes mellitus (T1DM) after a standardized liquid meal following insulin lispro (IL) or regular human insulin (RHI) given by microneedle-based intradermal (ID) versus subcutaneous (SC) delivery. Research Design and Methods: In this randomized, open-label, five-way crossover study, 29 T1DM patients received IL and RHI (0.125 U/kg) at 2 min and 17 min premeal, respectively, by both the SC and ID routes and also received RHI by the ID route at 2 min premeal. Blood glucose was stabilized at 120 mg/dL prior to a standardized 82-g carbohydrate liquid meal. ID delivery used a 34-gauge 1.5-mm steel microneedle, and SC delivery used a 31-gauge 8-mm syringe needle. Results: The 90-min PPG (blood glucose area under the curve for 0–1.5 h) for ID RHI was 14% lower than SC RHI at −17 min (P < 0.0001) and 11% lower than ID RHI at −2 min (P = 0.0006). PPG did not differ between ID RHI and SC IL, both at −2 min (P = 0.8345). ID IL PPG was lower than SC, both at −2 min, but not significantly (P = 0.10). Both ID IL and ID RHI PK data showed significantly faster uptake and time to maximum concentration, higher maximum concentration, and shorter systemic circulating duration versus SC dosing. ID IL and RHI delivery was generally well tolerated. Conclusions: 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.