BACKGROUND: Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery. METHOD: The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject's optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, -30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (-12 versus -2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl. RESULTS: The primary end point, postprandial time in range (70-180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (∆Tmax -16 min, ∆T50rising -7 min, ∆T50falling -30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90-120 min postprandially (∆12 mg/dl BG at 90 min, ∆7 mg/dl BGmax, ∆7 mg/dl mean BG 0-2 h, all p < .05). CONCLUSIONS: This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control.
RCT Entities:
BACKGROUND: Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery. METHOD: The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject's optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, -30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (-12 versus -2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl. RESULTS: The primary end point, postprandial time in range (70-180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (∆Tmax -16 min, ∆T50rising -7 min, ∆T50falling -30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90-120 min postprandially (∆12 mg/dl BG at 90 min, ∆7 mg/dl BGmax, ∆7 mg/dl mean BG 0-2 h, all p < .05). CONCLUSIONS: This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control.
Authors: Firas H El-Khatib; Steven J Russell; David M Nathan; Robert G Sutherlin; Edward R Damiano Journal: Sci Transl Med Date: 2010-04-14 Impact factor: 17.956
Authors: Linda Morrow; Douglas B Muchmore; Elizabeth A Ludington; Daniel E Vaughn; Marcus Hompesch Journal: Diabetes Technol Ther Date: 2011-06-29 Impact factor: 6.118
Authors: Julio Rosenstock; Daniel L Lorber; Luigi Gnudi; Campbell P Howard; David W Bilheimer; P-C Chang; Richard E Petrucci; Anders H Boss; Peter C Richardson Journal: Lancet Date: 2010-06-26 Impact factor: 79.321
Authors: Marcus Hompesch; Laura McManus; Roderike Pohl; Patrick Simms; Andreas Pfützner; Elena Bülow; Frank Flacke; Lutz Heinemann; Solomon S Steiner Journal: J Diabetes Sci Technol Date: 2008-07
Authors: K Rave; E Potocka; L Heinemann; T Heise; A H Boss; M Marino; D Costello; R Chen Journal: Diabetes Obes Metab Date: 2009-05-19 Impact factor: 6.577
Authors: Eda Cengiz; Stuart A Weinzimer; Jennifer L Sherr; Eileen M Tichy; Lori Carria; Darryll Cappiello; Amy Steffen; William V Tamborlane Journal: Diabetes Technol Ther Date: 2013-12-24 Impact factor: 6.118
Authors: Christopher Rini; Bruce C Roberts; Didier Morel; Rick Klug; Benjamin Selvage; Ronald J Pettis Journal: J Diabetes Sci Technol Date: 2019-03-17
Authors: James J Norman; Jyoti Gupta; Samirkumar R Patel; Sara Park; Courtney Jarrahian; Darin Zehrung; Mark R Prausnitz Journal: Drug Deliv Transl Res Date: 2014-04 Impact factor: 4.617
Authors: Dayu Lv; Sandip D Kulkarni; Alice Chan; Stephen Keith; Ron Pettis; Boris P Kovatchev; Leon S Farhi; Marc D Breton Journal: J Diabetes Sci Technol Date: 2015-03-09
Authors: Christopher James Rini; Elaine McVey; Diane Sutter; Stephen Keith; Heinz-Joerg Kurth; Leszek Nosek; Christoph Kapitza; Kerstin Rebrin; Laurence Hirsch; Ronald J Pettis Journal: Drug Deliv Transl Res Date: 2015-08 Impact factor: 4.617
Authors: Elena Matteucci; Ottavio Giampietro; Vera Covolan; Daniela Giustarini; Paolo Fanti; Ranieri Rossi Journal: Drug Des Devel Ther Date: 2015-06-17 Impact factor: 4.162