Authors: Satoshi Yoshiji, Masashi Hasebe, Yorihiro Iwasaki, Kimitaka Shibue, Yamato Keidai, Yohei Seno, Kanako Iwasaki, Sachiko Honjo, Jun Fujikawa & Akihiro Hamasaki
Abstract
Introduction
Previous studies suggested that β-cell function markers such as fasting and postprandial serum C-peptide and C-peptide increment (FCPR, PCPR, and ΔCPR, respectively) may be useful in estimating glycemic response to glucagon-like peptide-1 receptor agonists. However, it remains elusive whether baseline glycemic control confounds these markers. Here we aimed to identify the least confounded β-cell function markers and investigate whether these markers could predict glycemic response to dulaglutide.
Methods
We evaluated FCPR, PCPR, and ΔCPR levels in patients with type 2 diabetes who initiated dulaglutide treatment after a standardized meal tolerance test (MTT). We first investigated the confounding effects of baseline HbA1c on β-cell function markers using Pearson’s correlation test. Then, we evaluated the association between each β-cell function marker and glycemic response (HbA1c change 0–6 months) to dulaglutide using generalized linear model and logistic regression analysis with adjustment for baseline HbA1c.
Results
In 141 patients, baseline HbA1c was significantly inversely correlated with PCPR and ΔCPR (P < 0.01 for both) but not with FCPR (r = 0.02; P = 0.853), suggesting that FCPR was the marker least confounded by baseline glycemic control. Of all patients, 59 continued dulaglutide for at least 6 months without initiating any additional glucose-lowering medications. Mean ± SE HbA1c change 0–6 months was − 1.16 ± 0.17% (P < 0.001 vs. baseline). The β-cell function markers were significantly associated with HbA1c change 0–6 months in the generalized linear model. FCPR was also a significant predictor for achieving a reduction in HbA1c of at least 1% (P = 0.044) with an area under the receiver operating characteristic curve of 0.83 (sensitivity = 0.81 and specificity = 0.79).
Conclusion
Fasting and meal-induced C-peptide levels are associated with glycemic response to dulaglutide, among which FCPR is least confounded by baseline glycemic control, suggesting its utility as a marker for glycemic response to dulaglutide.
Key Summary Points |
Why carry out this study?Previous studies reported that β-cell function markers, such as fasting and meal-induced C-peptide levels, might be useful in estimating the efficacy of glucagon-like peptide-1 receptor agonists. However, the following questions remain unanswered: Are these markers confounded by baseline glycemic control, and if so, what is the least confounded marker? What is the association between that marker and glycemic response to dulaglutide, a widely used glucagon-like peptide-1 receptor agonists? We aimed to (i) investigate the confounding effect of baseline glycemic control on the β-cell function markers to determine the least confounded marker and (ii) investigate whether the β-cell function markers are associated with HbA1c-lowering effects of dulaglutide, exploring a suitable marker of glycemic response to dulaglutide. |
What was learned from this study?Meal-induced C-peptide levels (PCPR and ΔCPR) were significantly affected by baseline glycemic control, whereas fasting C-peptide (FCPR) was not, suggesting that FCPR was the marker least confounded by baseline glycemic control. FCPR, PCPR, and ΔCPR were significantly associated with glycemic response to dulaglutide. Furthermore, FCPR was a significant predictor for achieving a reduction in HbA1c of at least 1%, suggesting its utility as a marker for glycemic response to dulaglutide in clinical settings. |