Basal insulin peglispro demonstrates preferential hepatic versus peripheral action relative to insulin glargine in healthy subjects

Diabetes Care. 2014 Sep;37(9):2609-15. doi: 10.2337/dc14-0210. Epub 2014 Jun 19.


Objective: We evaluated the endogenous glucose production (EGP) and glucose disposal rate (GDR) over a range of doses of basal insulin peglispro (BIL) and insulin glargine in healthy subjects.

Research design and methods: This was a single-center, randomized, open-label, four-period, incomplete-block, crossover study conducted in eight healthy male subjects. Subjects had 8-h euglycemic clamps performed with primed, continuous infusions of BIL (5.1 to 74.1 mU/min) in three dosing periods and insulin glargine (20 or 30 mU/m(2)/min) in a fourth period, targeted to achieve 50-100% suppression of EGP. D-[3-(3)H] glucose was infused to assess rates of glucose appearance and disappearance.

Results: Mean BIL and insulin glargine concentrations (targeted to reflect the differences in intrinsic affinities of the two basal insulins) ranged from 824 to 11,400 and 212 to 290 pmol/L, respectively, and increased accordingly with increases in dose. Suppression of EGP and stimulation of GDR were observed with increasing concentrations of both insulins. At insulin concentrations where EGP was significantly suppressed, insulin glargine resulted in increased GDR. In contrast, at comparable suppression of EGP, BIL had minimal effect on GDR at lower doses and had substantially less effect on GDR than insulin glargine at higher doses.

Conclusions: The novel basal insulin analog BIL has relative hepatopreferential action and decreased peripheral action, compared with insulin glargine, in healthy subjects.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Cohort Studies
  • Cross-Over Studies
  • Glucose Clamp Technique
  • Healthy Volunteers
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics
  • Infusions, Intravenous
  • Insulin / administration & dosage*
  • Insulin / pharmacokinetics
  • Insulin Glargine
  • Insulin Lispro / administration & dosage
  • Insulin Lispro / analogs & derivatives*
  • Insulin Lispro / pharmacokinetics
  • Insulin, Long-Acting / administration & dosage*
  • Insulin, Long-Acting / pharmacokinetics
  • Liver / drug effects*
  • Male
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacokinetics
  • Young Adult


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Insulin, Long-Acting
  • basal insulin peglispro
  • Insulin Glargine
  • Polyethylene Glycols