Reply to the comment of Wilbrink et al. on Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes: The association between remaining β‐cell function and the achievement of the HbA1c target 1 year after initiation

Abstract

We have reported that the HbA1c‐lowering effects of liraglutide/basal insulin combination rely on remaining β‐cell function and that the cut‐off value of the C‐peptide immunoreactivity index (CPI), a β‐cell function‐related index frequently used in Japanese clinical settings, is 1.103 for the achievement of HbA1c <7.0% at 54 weeks after initiating the liraglutide/basal insulin combination. Wilbrink et al claimed that glucose‐lowering effects of glucagon‐like peptide‐1 receptor agonist liraglutide depend of duration of type 2 diabetes; while our resent study published in the Journal of Diabetes Investigation failed to detect such dependency. This discrepancy might be due to several reasons including co‐administration of basal insulin with liraglutide in our study; ethnic difference in T2D pathophysiology between the two study; and difference in sample size (The Usui study on liraglutide/basal insulin, n = 38; the Usui study on liraglutide monotherapy or SU combination, n=88; and the Wilbrink study, n = 69).

The Amount of Residual Incretin Regulates the Pancreatic β-cell Function and Glucose Homeostasis

“…At the onset of diabetes in this patient, his CPI was 0.7 and his ΔC-peptide on the glucagon loading test was 0.4 ng/ mL. The efficacy of GLP-1RA monotherapy or sulfonylurea combination depends on the remaining β-cell function (14). A ΔC-peptide on the glucagon loading test of 2.34 ng/mL or CPI of 1.86 have been reported as cut-off values for a longer therapeutic durability of initial GLP-1 RA in Japa-nese populations (15), suggesting that this particular case already possessed a reduced insulin secretory capacity at the initiation of GLP-1RA.…”