Exploring a Suitable Marker of Glycemic Response to Dulaglutide in Patients with Type 2 Diabetes: A Retrospective Study

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.