Aims: The effect of β-cell function on glycemic response to dulaglutide (DU) is not fully understood in clinical settings. We explored a suitable clinical marker of β-cell function to predict glycemic response to DU in patients with type 2 diabetes (T2D).
Methods: We retrospectively analyzed 141 patients who commenced once-weekly DU 0.75 mg after undergoing a meal tolerance test (MTT) with a standardized meal from September 2015 to December 2019 at our hospital. β-cell function was assessed by fasting and 2h postprandial serum C-peptide immunoreactivity (CPR) as well as increment of CPR (dCPR) in the MTT. We analyzed the suitability of each measurement as a marker for β-cell function and its association with glycemic response to DU using linear and logistic regression with adjustment for baseline HbA1c.
Results: In 141 patients, 2h postprandial CPR (PCPR) and dCPR showed significant inverse correlation with baseline HbA1c (r = -0.25 and -0.33, respectively; P < 0.01 for both), while fasting CPR (FCPR) did not (r = 0.02; P = 0.853). Given the association of high baseline HbA1c and impairment of meal-stimulated insulin secretion measured with PCPR and dCPR, we adopted FCPR as a marker for β-cell function with less influence from baseline HbA1c in the following analysis. Of the 141 patients, 59 patients continued DU without initiating any additional glucose-lowering agents for more than 6 months. The baseline mean ± SD HbA1c, fasting plasma glucose, and FCPR of the 59 patients were 8.9 ± 1.2%, 9.2 ± 2.3 mmol/L, 0.50 ± 0.29 nmol/L, respectively. The mean ± SE change in HbA1c 0-6 months was -1.2 ± 0.2%. FCPR was significantly associated with a reduction in HbA1c (P = 0.031). Furthermore, FCPR was a significant predictor for achieving a reduction in HbA1c ≥ 1% over 6 months (OR, 1.40; 95% CI, 1.14-1.71; P = 0.039) with the area under the receiver operating characteristics curve of 0.83.
Conclusions: FCPR is less affected by baseline HbA1c than PCPR and dCPR, and can be a useful marker for predicting glycemic response to DU.
M. Hasebe: None. S. Honjo: None. J. Fujikawa: None. A. Hamasaki: None. S. Yoshiji: None. Y. Iwasaki: None. S. Kimura: None. Y. Seno: None. Y. Keidai: None. T. Haraguchi: None. K. Iwasaki: None. Y. Wada: None.