Hypoglycemia Risk Related to Double Dose Is Markedly Reduced with Basal Insulin Peglispro Versus Insulin Glargine in Patients with Type 2 Diabetes Mellitus in a Randomized Trial: IMAGINE 8

Diabetes Technol Ther. 2017 Aug;19(8):463-470. doi: 10.1089/dia.2016.0414.

Abstract

Background: Basal insulin peglispro (BIL) has a peripheral-to-hepatic distribution of action that resembles endogenous insulin and a prolonged duration of action with a flat pharmacokinetic/pharmacodynamic profile at steady state, characteristics that tend to reduce hypoglycemia risk compared to insulin glargine (GL). The primary objective was to demonstrate that clinically significant hypoglycemia (blood glucose ≤54 mg/dL [3.0 mmol/L] or symptoms of severe hypoglycemia) occurred less frequently within 84 h after a double dose (DD) of BIL than a DD of GL.

Methods: This was a randomized, double-blind, two-period crossover study in patients with type 2 diabetes (T2D) previously treated with insulin (N = 68). For the first 3 weeks of each of the two crossover periods, patients received an individualized dose of BIL or GL once nightly (stable dose for 2 weeks/period). Then, during a 7-day inpatient stay with frequent blood glucose monitoring and standardized meals, one DD of study insulin was given. Glucose was infused if blood glucose was ≤54 mg/dL (3.0 mmol/L) or for symptoms of severe hypoglycemia.

Results: Within 84 h after the DD, a significantly smaller proportion of patients experienced clinically significant hypoglycemia with BIL compared to GL (BIL, 6.6%; GL, 35.5%; odds ratio for BIL/GL 0.13 [95% confidence interval 0.04-0.39]; P < 0.001). Adverse event profiles were similar for the two insulins. Serum alanine aminotransferase and triglyceride levels were significantly higher with BIL versus GL.

Conclusions: BIL has a markedly lower risk of hypoglycemia than GL when replicating a double-dose error in patients with T2D.

Keywords: Basal insulin peglispro (BIL); Fasting blood glucose; Hypoglycemia; Insulin therapy.; Type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / analysis*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / adverse effects*
  • Insulin Glargine / therapeutic use
  • Insulin Lispro / administration & dosage
  • Insulin Lispro / adverse effects
  • Insulin Lispro / analogs & derivatives*
  • Insulin Lispro / therapeutic use
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects*
  • Polyethylene Glycols / therapeutic use
  • Risk
  • Treatment Outcome
  • Young Adult

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin Lispro
  • basal insulin peglispro
  • Insulin Glargine
  • Polyethylene Glycols