A randomized clinical trial of basal insulin peglispro vs NPH in insulin-naïve patients with type 2 diabetes: the IMAGINE 6 trial

Diabetes Obes Metab. 2016 Oct:18 Suppl 2:34-42. doi: 10.1111/dom.12743.

Abstract

Aims: Basal insulin peglispro (BIL) has a longer duration of action than conventional insulin analogues and a hepato-preferential mechanism of action. This study assessed whether BIL was non-inferior to isophane insulin (NPH) in reducing HbA1c in insulin-naïve patients with type 2 diabetes, when added to pre-study oral anti-hyperglycaemic medications.

Materials and methods: This was a Phase 3, open-label, treat-to-target (TTT), randomized trial with a 2-week lead-in, 26-week treatment and a 4-week safety follow-up period. Patients were randomized to bedtime (pm) NPH, morning (am) BIL or pm BIL in a 1:1:1 ratio.

Results: Six hundred and forty-one patients [NPH, n = 213; BIL, n = 428 (am, n = 213; pm, n = 215)] received study drug. BIL was non-inferior to NPH for HbA1c change from baseline at Week 26 with a between-treatment difference (95% confidence interval) of -0.37% (-0.50, -0.23%). HbA1c at baseline was 8.5%, and was lower in BIL- vs NPH-treated patients after 26 weeks of treatment (6.8% vs 7.1%; P < .001). More BIL-treated patients achieved HbA1c <7.0% and HbA1c <7.0% without nocturnal hypoglycaemia. Fasting serum glucose levels and nocturnal hypoglycaemia rates were lower in BIL-treated patients; total hypoglycaemia rates were similar. Treatment-emergent adverse events were similar between groups. Fasting triglycerides decreased from baseline in both groups and to a greater extent with NPH, but were not significantly different between groups at Week 26. Mean alanine aminotransferase (ALT) increased with BIL treatment, but there was no evidence of acute severe hepatotoxicity.

Conclusions: In this TTT study, BIL treatment showed clinically relevant improvements in glycaemic control and a significant reduction in nocturnal hypoglycaemia compared to NPH.

Keywords: NPH; basal insulin peglispro; insulin-naïve; type 2 diabetes.

Publication types

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

MeSH terms

  • Aged
  • Alanine Transaminase / metabolism
  • Biguanides / therapeutic use
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Fasting
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Lispro / analogs & derivatives*
  • Insulin Lispro / therapeutic use
  • Insulin, Isophane / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • Triglycerides / metabolism

Substances

  • Biguanides
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Lispro
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Triglycerides
  • basal insulin peglispro
  • hemoglobin A1c protein, human
  • Polyethylene Glycols
  • Insulin, Isophane
  • Alanine Transaminase