Novel hepato-preferential basal insulin peglispro (BIL) does not differentially affect insulin sensitivity compared with insulin glargine in patients with type 1 and type 2 diabetes

Diabetes Obes Metab. 2017 Apr;19(4):482-488. doi: 10.1111/dom.12834. Epub 2017 Feb 7.


Aims: Basal insulin peglispro (BIL) is a novel PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and reduced peripheral effects, which results in a hepato-preferential action. In Phase 3 trials, patients with T1DM treated with BIL had lower prandial insulin requirements, yet improved prandial glucose control, relative to insulin glargine (GL). We hypothesized that this may be because of an enhanced sensitivity to prandial insulin with BIL resulting from lower chronic peripheral insulin action.

Materials and methods: Two open-label, randomized, 2-period crossover clinical studies were conducted in 28 patients with T1DM and 24 patients with T2DM. In each study period, patients received once-daily, individualized, stable, subcutaneous doses of BIL or GL for 5 weeks before a euglycaemic 2-step hyperinsulinemic clamp procedure (with [6,6- 2 H2 ]-glucose in 12 of the patients with T1DM). M-values were derived from the clamp procedure for all patients, with rate of glucose appearance (Ra) and disappearance (Rd) and insulin sensitivity index (SI) determined from the clamps with [6,6- 2 H2 ]-glucose.

Results: There were no statistically significant differences between BIL and GL in key measures of hepatic (% Ra suppression during the low-dose insulin infusion; 78.7% with BIL, 81.8% with GL) or peripheral (M-value and M/I during the high-dose insulin infusion, Rd and SI) insulin sensitivity in patients with T1DM or T2DM.

Conclusions: The need to reduce prandial insulin observed with BIL during phase 3 trials cannot be explained by the differential effects of BIL and GL on sensitivity to prandial insulin in either T1DM or T2DM.

Keywords: Phase 1 to 2 study; basal insulin; drug mechanism; insulin resistance; type 1 diabetes; type 2 diabetes.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Glucose Clamp Technique
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Glargine / administration & dosage*
  • Insulin Lispro / administration & dosage
  • Insulin Lispro / analogs & derivatives*
  • Insulin Resistance / physiology*
  • Liver / drug effects
  • Liver / physiopathology
  • Male
  • Meals
  • Metformin / administration & dosage
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Lispro
  • basal insulin peglispro
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • Polyethylene Glycols
  • Metformin