Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control in patients with diabetes

Elsemiek E C Engwerda, Cees J Tack, Bastiaan E de Galan, Elsemiek E C Engwerda, Cees J Tack, Bastiaan E de Galan

Abstract

Objective: Clamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes.

Research design and methods: In a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles.

Results: Insulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L(-1); P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes.

Conclusions: The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.

Figures

Figure 1
Figure 1
Changes from baseline during the standardized meal test. A: Changes in plasma insulin levels after insulin administration by jet injector (○) and conventional pen (■). B: Changes in plasma glucose levels after insulin administration by jet injector (○) and conventional pen (■).
Figure 2
Figure 2
The 2-h BG-AUC values for the jet injector (white bars) and conventional pen (black bars) in subgroups according to type of diabetes.

References

    1. Monnier L, Colette C, Owens D. Postprandial and basal glucose in type 2 diabetes: assessment and respective impacts. Diabetes Technol Ther 2011;13(Suppl. 1):S25–S32
    1. Siebenhofer A, Plank J, Berghold A, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev 2006;19:CD003287.
    1. Rassam AG, Zeise TM, Burge MR, Schade DS. Optimal administration of lispro insulin in hyperglycemic type 1 diabetes. Diabetes Care 1999;22:133–136
    1. Peyrot M, Rubin RR, Kruger DF, Travis LB. Correlates of insulin injection omission. Diabetes Care 2010;33:240–245
    1. Gale EA. Two cheers for inhaled insulin. Lancet 2001;357:324–325
    1. Peyrot M, Rubin RR. Levels and risks of depression and anxiety symptomatology among diabetic adults. Diabetes Care 1997;20:585–590
    1. Aronson R. The role of comfort and discomfort in insulin therapy. Diabetes Technol Ther 2012;14:741–747
    1. Malone JI, Lowitt S, Grove NP, Shah SC. Comparison of insulin levels after injection by jet stream and disposable insulin syringe. Diabetes Care 1986;9:637–640
    1. Mitragotri S. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov 2006;5:543–548
    1. Engwerda EE, Abbink EJ, Tack CJ, de Galan BE. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care 2011;34:1804–1808
    1. Abumrad NN, Rabin D, Diamond MP, Lacy WW. Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man. Metabolism 1981;30:936–940
    1. de Galan BE, Tack CJ, Lenders JW, et al. Theophylline improves hypoglycemia unawareness in type 1 diabetes. Diabetes 2002;51:790–796
    1. de Galan BE, Engwerda EE, Abbink EJ, Tack CJ. Body mass index and the efficacy of needle-free jet injection for the administration of rapid-acting insulin analogs, a post hoc analysis. Diabetes Obes Metab 2013;15:84–86
    1. Radermecker RP, Renard E, Scheen AJ. Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control. Diabetes Metab Res Rev 2009;25:491–501
    1. Vora JP, Burch A, Peters JR, Owens DR. Relationship between absorption of radiolabeled soluble insulin, subcutaneous blood flow, and anthropometry. Diabetes Care 1992;15:1484–1493
    1. McQuaid SE, Humphreys SM, Hodson L, Fielding BA, Karpe F, Frayn KN. Femoral adipose tissue may accumulate the fat that has been recycled as VLDL and nonesterified fatty acids. Diabetes 2010;59:2465–2473
    1. Hildebrandt P. Skinfold thickness, local subcutaneous blood flow and insulin absorption in diabetic patients. Acta Physiol Scand Suppl 1991;603:41–45
    1. Vora JP, Burch A, Peters JR, Owens DR. Absorption of radiolabelled soluble insulin in type 1 (insulin-dependent) diabetes: influence of subcutaneous blood flow and anthropometry. Diabet Med 1993;10:736–743
    1. Tobin L, Simonsen L, Bülow J. The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes. Clin Physiol Funct Imaging 2011;31:458–463
    1. Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Factors associated with injection omission/non-adherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Obes Metab 2012;9999:1081–1087
    1. Schramm J, Mitragotri S. Transdermal drug delivery by jet injectors: energetics of jet formation and penetration. Pharm Res 2002;19:1673–1679
    1. Stachowiak JC, Li TH, Arora A, Mitragotri S, Fletcher DA. Dynamic control of needle-free jet injection. J Control Release 2009;135:104–112
    1. Schramm-Baxter J, Mitragotri S. Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power. J Control Release 2004;97:527–535
    1. Linn L, Boyd B, Iontchev H, King T, Farr SJ. The effects of system parameters on in vivo injection performance of a needle-free injector in human volunteers. Pharm Res 2007;24:1501–1507
    1. Raz I, Weiss R, Yegorchikov Y, Bitton G, Nagar R, Pesach B. Effect of a local heating device on insulin and glucose pharmacokinetic profiles in an open-label, randomized, two-period, one-way crossover study in patients with type 1 diabetes using continuous subcutaneous insulin infusion. Clin Ther 2009;31:980–987
    1. Muchmore DB, Vaughn DE. Review of the mechanism of action and clinical efficacy of recombinant human hyaluronidase coadministration with current prandial insulin formulations. J Diabetes Sci Tech 2010;4:419–428
    1. Steiner S, Hompesch M, Pohl R, et al. A novel insulin formulation with a more rapid onset of action. Diabetologia 2008;51:1602–1606

Source: PubMed

3
Subskrybuj