title: Stability and performance of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion: a systematic review.
abstract: OBJECTIVE
  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.
authors.affiliation: Bournemouth Diabetes and Endocrine Centre, Royal Bournemouth Hospital NHS Foundation Trust, Dorset, UK. david.kerr@rbch.nhs.uk.
authors.forename: David
authors.initials: D
authors.lastname: Kerr
authors.forename: Erik
authors.initials: E
authors.lastname: Wizemann
authors.forename: Jakob
authors.initials: J
authors.lastname: Senstius
authors.forename: Mette
authors.initials: M
authors.lastname: Zacho
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Ampudia-Blasco
mesh_terms: D000595:Amino Acid Sequence; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004355:Drug Stability; D006801:Humans; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061267:Insulin Aspart / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007332:Insulin Infusion Systems / Q000009:adverse effects; D061268:Insulin Lispro / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061266:Insulin, Short-Acting / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007328:Insulin; D061268:Insulin Lispro; D061266:Insulin, Short-Acting; C479079:insulin glulisine; D061267:Insulin Aspart