Factors Affecting the Absorption of Subcutaneously Administered Insulin: Effect on Variability

Abstract

Variability in the effect of subcutaneously administered insulin represents a major challenge in insulin therapy where precise dosing is required in order to achieve targeted glucose levels. Since this variability is largely influenced by the absorption of insulin, a deeper understanding of the factors affecting the absorption of insulin from the subcutaneous tissue is necessary in order to improve glycaemic control and the long-term prognosis in people with diabetes. These factors can be related to either the insulin preparation, the injection site/patient, or the injection technique. This review highlights the factors affecting insulin absorption with special attention on the physiological factors at the injection site. In addition, it also provides a detailed description of the insulin absorption process and the various modifications to this process that have been utilized by the different insulin preparations available.

Figure 1

An overview of the layers of the skin and muscle. Upon injection into the subcutaneous compartment, insulin can either be absorbed by blood capillaries (red) and/or lymphatic capillaries (green). Adapted with permission from Taylor & Francis and Frost GI: Recombinant human hyaluronidase (rHuPH20): An enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv (2007) 4(4):427–440. © 2007 Taylor & Francis.

Figure 2

Relationship between the insulin oligomers (monomers, dimers, and hexamers) and the equilibrium constants K_DH and K_MD. Adapted and printed with permission from Elsevier and Rasmussen: Insulin aspart pharmacokinetics: an assessment of its variability and underlying mechanisms. Eur J Pharm Sci (2014) 62: 65–75. © 2014 Elsevier.

Figure 3

Relative abundance (%) of insulin hexamers, dimers, and monomers as a function of total concentration C_τ. Printed with permission from Elsevier and Søeborg: Absorption kinetics of insulin after subcutaneous administration. Eur J Pharm Sci (2009) 36: 78–90. © 2009 Elsevier.