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. 2013 Nov 1;7(6):1595-606.
doi: 10.1177/193229681300700620.

Stability and performance of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion: a systematic review

David Kerr  1 , Erik Wizemann, Jakob Senstius, Mette Zacho, Francisco Javier Ampudia-Blasco
Affiliations

Stability and performance of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion: a systematic review

David Kerr et al. J Diabetes Sci Technol. .

Abstract

Aim: We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes.

Methods: Two predefined search strategies were systematically implemented to search Medline and the Cochrane Register of Clinical Trials for publications between 1996 and 2012.

Results: Twenty studies were included in the review: 13 in vitro studies and 7 clinical studies. In vitro studies investigated the effects of extreme CSII conditions (high temperature and mechanical agitation) on the risk of catheter occlusions and insulin stability factors, such as potency, purity, high molecular weight protein content, pH stability, and preservative content (m-cresol, phenol). Under these conditions, the overall stability of rapid-acting insulin analogs was similar for insulin lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed greater susceptibility to insulin precipitation and catheter occlusions. A limited number of clinical trials were identified; this evidence-based information suggests that the rate of catheter occlusions in patients with type 1 diabetes using CSII treatment may vary depending on the rapid-acting analog used.

Conclusions: Based on a limited amount of available data, the safety, stability, and performance of the three available rapid-acting insulin analogs available for use with CSII were similar. However, there is limited evidence suggesting that the risk of occlusion may vary with the insulin preparation under certain circumstances.

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Figures

Figure 1.
Figure 1.
Fibrillation process. Reprinted (adapted) with permission from Nielsen L, Frokjaer S, Brange J, Uversky VN, Fink AL. Biochemistry. 2001;40:8397–409. Copyright 2001 American Chemical Society.
Figure 2.
Figure 2.
Primary structure of rapid-acting insulin analogs. Further information can be found at www.humalog.com (Eli Lilly & Company; revised May 2011), www.apidra.com (Sanofi-Aventis; revised February 2009), and www.novolog.com (Novo Nordisk; revised June 2011). Ala, alanine; Arg, arginine; Asn, asparagine; Asp, aspartic acid; Cys, cysteine; Gln, glutamine; Glu, glutamic acid; Gly, glycine; His, histidine; Ile, isoleucine; Leu, leucine; Lys, lysine; Phe, phenylalanine; Pro, proline; Ser, serine; Thr, threonine; Tyr, tyrosine; Val, valine.
Figure 3.
Figure 3.
Medline search strategies. AE, adverse event; CGM, continuous glucose monitoring; PK/PD, pharmacokinetics/pharmacodynamics.
See this image and copyright information in PMC

References

    1. Pickup J. Insulin pumps. Int J Clin Pract Suppl. 2011;170:16–19. - PubMed
    1. Siebenhofer A, Plank J, Berghold A, Jeitler K, Horvath K, Narath M, Gfrerer R, Pieber TR. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev. 2006;2:CD003287. - PubMed
    1. Bolli GB, Di Marchi RD, Park GD, Pramming S, Koivisto VA. Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia. 1999;42(10):1151–1167. - PubMed
    1. Anderson JH, Jr, Brunelle RL, Koivisto VA, Pfützner A, Trautmann ME, Vignati L, DiMarchi R. Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group. Diabetes. 1997;46(2):265–270. - PubMed
    1. Hoogma RP, Schumicki D. Safety of insulin glulisine when given by continuous subcutaneous infusion using an external pump in patients with type 1 diabetes. Horm Metab Res. 2006;38(6):429–433. - PubMed

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