Effect of once weekly dulaglutide by baseline beta-cell function in people with type 2 diabetes in the AWARD programme

Diabetes Obes Metab. 2018 Aug;20(8):2023-2028. doi: 10.1111/dom.13313. Epub 2018 May 2.

Abstract

Glucagon-like peptide-1 receptor agonists lower blood glucose in type 2 diabetes (T2D) partially through glucose-dependent stimulation of insulin secretion. The aim of this study was to investigate whether beta-cell function (as measured by HOMA2-%B) at baseline affects the glycaemic response to dulaglutide. Dulaglutide-treated patients from AWARD-1, AWARD-3 and AWARD-6 clinical studies were categorised based on their homeostatic model assessment of beta-cell function (HOMA2-%B) tertiles. Changes in glycaemic measures in response to treatment with once-weekly dulaglutide were evaluated in each HOMA2-%B tertile. Patients with low HOMA2-%B had higher baseline glycated haemoglobin (HbA1c), fasting and postprandial blood glucose, and longer duration of diabetes (P < .001, all) (mean low, middle and high tertiles with dulaglutide 1.5 mg: HOMAB-2%B, 31%, 58%, 109%; HbA1c, 8.7%, 7.7%, 7.3%, respectively). At 26 weeks, the low tertile experienced larger reductions in HbA1c compared to the high tertile with dulaglutide 1.5 mg (mean; -1.55% vs. -0.98% [-16.94 vs. -10.71 mmol/mol]). Differences between low and high tertiles disappeared when adjusted for baseline HbA1c (LSM; -1.00 vs. -1.18% [-10.93 vs. -12.90 mmol/mol]). Greater decreases in fasting blood glucose and greater increases in fasting C-peptide were observed in the low tertile. Similar increases in HOMA2-%B were observed in all tertiles. Dulaglutide demonstrated clinically relevant HbA1c reduction irrespective of estimated baseline beta-cell function.

Keywords: GLP-1 receptor agonist; beta-cell function; dulaglutide; type 2 diabetes.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Peptide / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / therapeutic use
  • Immunoglobulin Fc Fragments / administration & dosage*
  • Immunoglobulin Fc Fragments / therapeutic use
  • Insulin Resistance*
  • Insulin Secretion / drug effects
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / therapeutic use

Substances

  • Biomarkers
  • C-Peptide
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptides
  • dulaglutide