Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonist dulaglutide in combination with prandial insulin lispro: an AWARD-4 substudy

Diabetes Obes Metab. 2016 Oct;18(10):999-1005. doi: 10.1111/dom.12705. Epub 2016 Jul 22.

Abstract

Aim: To conduct a substudy, using 24-hour continuous glucose monitoring (CGM), of the AWARD-4 trial, which was designed to compare insulin + glucagon-like peptide-1 receptor agonist treatment with an insulin-only regimen.

Methods: The AWARD-4 trial randomized 884 conventional insulin regimen-treated patients to dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM substudy included 144 patients inserted with a Medtronic CGMS iPro CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26 and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia and glucose variability. The primary objective was treatment comparison for percentage time spent with CGM glucose values in the 3.9-7.8 mmol/L range after 26 weeks.

Results: At week 26, mean CGM values decreased in all treatment groups (change from baseline -2.8 ± 0.3, -2.4 ± 0.3 and -2.5 ± 0.3 mmol/L for dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in the 3.9-7.8 mmol/L range. Percentage time in the 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than for glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. The overall within-patient standard deviation (s.d.) was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences among the groups with regard to measures of normoglycaemia or near-normoglycaemia and for the overall within-patient s.d. Treatment with glargine was associated with greater increases in percentage time spent with glucose values ≤3.9 mmol/L, with statistically significant differences between the groups at 52 weeks (p < 0.05).

Conclusions: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range.

Keywords: continuous glucose monitoring; dulaglutide; glargine; type 2 diabetes.

Publication types

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

MeSH terms

  • Aged
  • Blood Glucose / analysis*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Glucose Self-Monitoring / methods
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / adverse effects
  • Glucagon-Like Peptides / analogs & derivatives*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Immunoglobulin Fc Fragments / administration & dosage*
  • Immunoglobulin Fc Fragments / adverse effects
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / adverse effects
  • Insulin Lispro / administration & dosage*
  • Insulin Lispro / adverse effects
  • Male
  • Meals
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / adverse effects

Substances

  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Insulin Lispro
  • Recombinant Fusion Proteins
  • Insulin Glargine
  • Glucagon-Like Peptides
  • dulaglutide