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

McVey, Elaine; Hirsch, Laurence; Sutter, Diane; Kapitza, Christoph; Dellweg, Sibylle; Clair, Janina; Rebrin, Kerstin; Judge, Kevin; Pettis, Ronald J.

doi:10.1177/193229681200600403

Cited by 39 publications

(39 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Without comparable (i.e., identical) glucose/insulin levels in the last hour(s) prior to the intervention (i.e., ingestion of the meal/insulin application), the validity of comparing the results obtained on different study days is compromised. With the UFIs presented here, some meal-related studies fulfilling these requirements have been performed demonstrating their benefits also in comparison with RAIAs (see the other related manuscripts 18,25,30,48,49,54 ). One can envisage head-to-head comparisons involving two or more of the approaches presented in a given study under identical UFI conditions that would allow one to make clear statements about the pros and cons of the studied developments.…”

Section: Discussion and Outlookmentioning

confidence: 99%

See 1 more Smart Citation

Ultrafast-Acting Insulins: State of the Art

Heinemann

Muchmore

2012

J Diabetes Sci Technol

View full text Add to dashboard Cite

Abbreviations: (AP) artificial pancreas, (ARIA) alternative routes of insulin administration, (CGM) continuous glucose monitoring, (CSII) continuous subcutaneous insulin infusion, (FDA) Food and Drug Administration, (GIR) glucose infusion rate, (GV) glycemic variability, (HbA1c) hemoglobin A1c, (HGP) hepatic glucose production, (ID) intradermal, (IMI) injection-meal interval, (NDA) new drug application, (PD) pharmacodynamic, (PK) pharmacokinetic, (PPG) postprandial glycemic excursion, (RAIA) rapid-acting insulin analog, (RHI) regular human insulin, (rHuPH20) recombinant human hyaluronidase, (SC) subcutaneous, (T1DM) type 1 diabetes mellitus, (T2DM) type 2 diabetes mellitus, (TI) Technosphere insulin, (UFI) ultrafast-acting insulin

show abstract

Section: Discussion and Outlookmentioning

confidence: 99%

“…The U.S.-based company Becton Dickinson (see the article by McVey and coworkers 25 in this special theme issue) is developing an insulin infusing product that applies the insulin by means of short insulin needles ("microneedles") into the dermis instead of the SC tissue.…”

Section: Intradermal Application Of the Insulinmentioning

confidence: 99%

Ultrafast-Acting Insulins: State of the Art

Heinemann

Muchmore

2012

J Diabetes Sci Technol

View full text Add to dashboard Cite

show abstract

“…[20][21][22][23] Alternative insulin delivery methods such as inhaled insulin and intradermal delivery with microneedles have been shown to confer ultra-fast-acting profiles during meal and insulin clamp studies. [24][25][26] Further studies are needed to determine whether the time-action profiles of rapid-acting insulin analogs can be accelerated even more by combining site warming with one or another of these alternative approaches.…”

Section: Discussionmentioning

confidence: 99%

Faster In and Faster Out: Accelerating Insulin Absorption and Action by Insulin Infusion Site Warming

Cengiz

Weinzimer²,

Sherr³

et al. 2014

Diabetes Technology & Therapeutics

View full text Add to dashboard Cite

Objective: This study was undertaken to investigate the effect of an insulin infusion site warming device, the InsuPatch 40 Ô (IP 40 ) (InsuLine Medical Ltd., Petach-Tikvah, Israel), on insulin aspart pharmacodynamics (PD) and pharmacokinetics (PK) in adolescents with type 1 diabetes. Subjects and Methods: Seventeen subjects with type 1 diabetes (age, 15 -1 years; hemoglobin A1c, 7.5 -0.2% [58 -2.2 mmol/ mol]) underwent two euglycemic clamps performed on separate mornings with and without IP 40 activation with warming temperature at 40°C. On both days, the basal infusion was suspended, and glucose levels were maintained between 90 and 100 mg/dL by a variable rate dextrose infusion for up to 5 h after a 0.2 U/kg bolus of insulin aspart. Results: Time to peak insulin action and time to half-maximal action occurred earlier with a greater early glucodynamic effect (area under the curve [AUC] for glucose infusion rate from 0 to 30 min) with IP 40 than without the IP 40 , whereas the AUC for the time-action profile and the peak action did not differ with and without infusion site warming. PK parameters were in agreement with PD parameters, namely, a significantly earlier time to reach the maximum increment in insulin concentrations and greater early bioavailability (AUC for the change in insulin concentration from 0 to 30 min) with the IP 40 . The tail of the plasma insulin response curve was also shortened with infusion site warming, with the time to reach baseline insulin concentration occurring significantly earlier (P = 0.04).Conclusions: Our data demonstrate that skin warming around the infusion site to 40°C with the IP 40 is an effective means to accelerate absorption and action of rapid-acting insulin. These improvements in time-action responses have the potential to enhance the performance of open-and closed-loop insulin delivery systems.

show abstract

“…These include micro-needle, intradermal infusion sets for pump therapy, [12][13][14][15] changes in excipients in RAIA formulations to accelerate insulin molecule monomerization 16 and treating the insulin infusion site with hyaluronidase to breakdown interstitial barriers to dispersion of injected liquids. 17 In comparison to these approaches, local warming relies on a relatively simple physiological approach which, in this study, we have demonstrated is suited for injection as well as pump therapy.…”

Section: Discussionmentioning

confidence: 99%

Improved Postprandial Glucose Control Using the InsuPad Device in Insulin-Treated Type 2 Diabetes

Bitton¹,

Feldman²,

A³

et al. 2015

J Diabetes Sci Technol

View full text Add to dashboard Cite

Exaggerated postprandial glycemic excursions in the first hours after a meal and an increased risk of late postprandial hypoglycemia are commonly observed following bolus injections of regular human insulin due to the delayed peak and the prolonged duration of action of this insulin preparation. 1 In contrast, plasma insulin concentrations peak earlier (generally thought to be within the first hour) and plasma insulin concentrations return to baseline more quickly with rapid-acting insulin analogs (RAIAs).2 Nevertheless, even with the more favorable absorption characteristics of RAIAs, postmeal hyperglycemia remains difficult to control in insulin-requiring diabetic patients due to delays in the peak action of these analogs to 120 or more minutes after injection. The time to peak insulin concentrations following bolus injections of both human regular and RAIAs are dose dependent, 3 with higher doses leading to delayed peaks and prolonged duration of action of these insulins. Moreover, the FDA-approved prescribing information package inserts for RAIAs state that the time course of action of these insulins may vary in different individuals or at different times in the same individual. 4 Such variations in insulin action are dependent on many conditions, including the site of injection, local blood supply and local skin temperature. 4 The impact of the site of injection on the rate of absorption of regular insulin (ie, abdomen > arm > leg) was first described by Koivisto and Felig in 1980. 5 They also demonstrated that increasing the skin temperature to 30°C to 37°C via sauna use increased the rate of insulin absorption and 578881D STXXX10.1177/1932296815578881Journal Abstract Background: Delays in the time-action profiles of premeal boluses of rapid-acting insulin analogs contribute to early postmeal hyperglycemia in patients with diabetes. We tested whether applying local heat to skin around the injection site to increase the rate of insulin absorption reduces postprandial hyperglycemia in patients with type 2 diabetes. Methods: Fourteen patients with type 2 diabetes (4 females; age 61.6 ± 8.4 years, HbA1c 8.42 ± 1.13%; BMI 29.10 ± 5.61 kg/m 2 ) on intensified insulin therapy underwent 5-hour meal tolerance tests (MTTs) with a standardized liquid meal after an overnight fast on 2 study days. Subjects injected 0.2 U/kg of insulin aspart or lispro subcutaneously into the abdominal skin on both days with and without the use of the InsuPad device. Results: Following the premeal bolus injection of rapid-acting insulin analog, infusion site warming led to a rise in plasma insulin levels to peak concentrations that were significantly earlier than without skin warming (mean ± SD 52 ± 26.7 vs 80 ± 51.3 minutes, P < .005) as well as increase in plasma insulin levels during the first hour after injection (mean ± SD 63.5 ± 32.7 IU vs 48.0 ± 25.0 uU.min/ml, P = .019). As a result, the area under the curve of the postprandial glucose excursion during the first 2 hours (the primary study outcome) and the entire 5 hours after ...

show abstract

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

Abstract: 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.

Cited by 39 publications

References 46 publications

Ultrafast-Acting Insulins: State of the Art

Ultrafast-Acting Insulins: State of the Art

Faster In and Faster Out: Accelerating Insulin Absorption and Action by Insulin Infusion Site Warming

Improved Postprandial Glucose Control Using the InsuPad Device in Insulin-Treated Type 2 Diabetes

Contact Info

Product

Resources

About