title: The development of new basal insulins: is there any clinical advantage with their use in type 2 diabetes?
abstract: BACKGROUND
  The basal insulin products currently on market do not optimally mimic endogenous insulin secretion. These unmet clinical needs have fueled the development of new basal insulin analogues for improving their pharmacokinetics/pharmacodynamics profile.
  
  
  METHODS
  We review the recent literature investigating the efficacy and safety of new basal insulin analogues in type 2 diabetes, as in the USA, insulin utilization accounted for 26% of treatment visits for these patients in 2012. Insulin degludec is a desB30 insulin acylated at the LysB29 residue with a glutamate linker and 16-carbon fatty diacyl side chain. Insulin lispro has been PEGylated at lysine B28, via a urethane bond, which increases the hydrodynamic size of the molecule and reduces its absorption and clearance following subcutaneous administration. Glargine U300 represents a new high-strength glargine formulation (300 U/ml): once injected, U300 forms a compact subcutaneous depot with a smaller surface area to produce a more gradual and prolonged release. Both PEG-lispro and glargine U300 are not yet on the market.
  
  
  CONCLUSIONS
  Ultra-long acting and high-strength formulations of new basal analogues have the potential for less glycemic variability, less (nocturnal) hypoglycemia and weight-loss advantage for PEG-lispro. However, these new basal insulin analogues need to be monitored closely for adverse signals.
authors.affiliation: Second University of Naples, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging , Naples , Italy.
authors.forename: Maria Ida
authors.initials: MI
authors.lastname: Maiorino
authors.forename: Michela
authors.initials: M
authors.lastname: Petrizzo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capuano
authors.forename: Dario
authors.initials: D
authors.lastname: Giugliano
authors.forename: Katherine
authors.initials: K
authors.lastname: Esposito
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D061385:Insulins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D061268:Insulin Lispro; D049528:Insulin, Long-Acting; D061385:Insulins; C587357:LY2605541; D000069036:Insulin Glargine; D011092:Polyethylene Glycols; C571886:insulin degludec
keywords: basal insulin analogues; clinical advantage; insulin therapy; type 2 diabetes