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

Aims: The GLP-1 receptor agonist liraglutide improves impaired pancreatic beta-cell function, thereby exerting glucose-lowering effects. However, the association of remaining beta-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 beta-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-Delta CPR) with achievement of HbA1c <7.0% at 54 weeks after liraglutide initiation. Results: Among 165 subjects continuing liraglutide for 54 weeks, 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 54 weeks, while 49 subjects did not. Subjects achieving HbA1c <7.0% showed higher values of GST-Delta CPR. Receiver-operating analysis revealed 2.34 ng/mL as the cut-off value for HbA1c <7.0% achievement in these subjects. Subjects with GST-Delta CPR >2.34 ng/mL showed continuous and substantial HbA1c reduction throughout the 54 weeks. In Kaplan-Meier analysis, subjects with GST-Delta CPR >2.34 ng/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 beta-cell function at initiation. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.