Retrospective analysis of safety and efficacy of liraglutide monotherapy and sulfonylurea-combination therapy in Japanese type 2 diabetes: Association of remaining β-cell function and achievement of HbA1c target one year after initiation

J Diabetes Complications. 2015 Nov-Dec;29(8):1203-10. doi: 10.1016/j.jdiacomp.2015.07.020. Epub 2015 Jul 21.

Abstract

Aims: The GLP-1 receptor agonist liraglutide improves impaired pancreatic β-cell function, thereby exerting glucose-lowering effects. However, the association of remaining β-cell function with long-term therapeutic efficacy of liraglutide remains largely unknown.

Methods: Patients with type 2 diabetes who started liraglutide as monotherapy or sulfonylurea-combination therapy were retrospectively analyzed to identify possible associations of indices related to β-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-ΔCPR) with achievement of HbA1c <7.0% at 54weeks after liraglutide initiation.

Results: Among 165 subjects continuing liraglutide for 54weeks, 66 received additional oral anti-diabetic drugs (OADs) during the period. Of those continuing liraglutide without receiving additional OADs, 41 subjects achieved HbA1c <7.0% at 54weeks, while 49 subjects did not. Subjects achieving HbA1c <7.0% showed higher values of GST-ΔCPR. Receiver-operating analysis revealed 2.34ng/mL as the cut-off value for HbA1c <7.0% achievement in these subjects. Subjects with GST-ΔCPR >2.34ng/mL showed continuous and substantial HbA1c reduction throughout the 54weeks. In Kaplan-Meier analysis, subjects with GST-ΔCPR >2.34ng/mL showed longer therapeutic durability of initial liraglutide therapy with no additional OADs or insulin.

Conclusions: Despite numerous limitations, these results indicate that long-term efficacy of liraglutide is associated with remaining β-cell function at initiation.

Keywords: C-peptide; GLP-1 receptor agonist; Glucagon stimulation test; Type 2 diabetes; β-Cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Monitoring
  • Drug Resistance
  • Drug Therapy, Combination / adverse effects
  • Female
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Incretins / adverse effects
  • Incretins / therapeutic use
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Japan
  • Kaplan-Meier Estimate
  • Liraglutide / adverse effects*
  • Liraglutide / therapeutic use
  • Male
  • Middle Aged
  • ROC Curve
  • Retrospective Studies
  • Sulfonylurea Compounds / adverse effects*
  • Sulfonylurea Compounds / therapeutic use

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Incretins
  • Insulin
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Liraglutide
  • Glucagon-Like Peptide-1 Receptor Agonists