Differential HbA1c response in the placebo arm of DPP-4 inhibitor clinical trials conducted in China compared to other countries: a systematic review and meta-analysis.
It has been observed that the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors as compared to the placebo groups in some clinical trials conducted in China is weaker than that in trials conducted outside China, leading to the suspicion that this may be caused by differential Glycosylated Hemoglobin (HbA1c) response in the placebo arm of DPP-4 inhibitor clinical trials conducted in China compared to other countries.



We searched published articles and other documents related to phase III placebo-control trials of DPP-4 inhibitors in Type 2 diabetes mellitus (T2DM). We included studies from different countries and compared those conducted in China to those conducted in other countries. Meta-regression analysis was used to analyze the HbA1c response in the placebo arms.



A total of 66 studies met the inclusion criteria and 10 were conducted within China. There were a total of 8303 participants (mean age 56, male 57 %) in placebo groups. The pooled change in HbA1c for the placebo groups of 10 trials conducted in patients with T2DM in China was 0.26 % (95 % CI [-0.36 %, -0.16 %], p-value < 0.001), compared to 0.015 % (95 % CI [-0.05 %, 0.08 %], p-value is 0.637) for 56 trials conducted outside of China. The difference of placebo effect between trials conducted in and outside China is -0.273 % (95 % CI [-0.42 %, -0.13 %], p-value is less than 0.001) while after excluding trials conducted in Japan, the difference is -0.203 % (95 % CI [-0.35 %, -0.06 %], p-value is 0.005). They are both statistically significant.



The meta-analysis in the article demonstrates that there is statistically significant difference in the HbA1c response in the placebo arm of DPP-4 inhibitor clinical trials conducted in China compared to other countries. This differential HbA1c response in the placebo arm should be taken into consideration by both experimenters and medical decision makers when future DPP-4 studies are conducted in China.
Research School of Finance, Actuarial Studies & Statistics, The Australian National University, Canberra, ACT 2601, Australia.
Lingyu
L
He
Clinical Research, MSD China R&D Center, Beijing, 100015, China.
Shu
S
Liu
National Institutes for Food and Drug Control, Beijing, 100050, China.
Chun
C
Shan
Clinical Research, MSD China R&D Center, Beijing, 100015, China.
Yingmei
Y
Tu
MSD China R&D Center, Beijing, 100015, China.
Zhengqing
Z
Li
Faculty of Health Sciences, University of Macau, Taipa, Macau. DouglasZhang@umac.mo.
Xiaohua Douglas
XD
Zhang
D000284:Administration, Oral; D002681:China / Q000453:epidemiology; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016896:Treatment Outcome
D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
Diabetes mellitus; Differential HbA1c response; Dipeptidyl peptidase-4 inhibitor; Meta-analysis; T2DM