Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2020; 11(12): 654-665
Published online Dec 15, 2020. doi: 10.4239/wjd.v11.i12.654
Exenatide once weekly combined with metformin reduced glycemic variability in type 2 diabetes by using flash glucose monitoring system
Yang Li, Min-Min Han, Qiong He, Zi-Ang Liu, Dong Liang, Jing-Tian Hou, Yi Zhang, Yun-Feng Liu
Yang Li, Min-Min Han, Qiong He, Dong Liang, Jing-Tian Hou, Yun-Feng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Zi-Ang Liu, Department of First Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Yi Zhang, Department of Pharmacology, Basic Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Author contributions: Liu YF and Zhang Y designed the study and revised the manuscript; Li Y and Han MM drafted the initial manuscript; Li Y, Han MM, and He Q analyzed and interpreted the data; Liu ZA, Liang D, Hou JT, Li Y, Han MM, and He Q conducted the study and collected the data. All authors read and approved the final manuscript for publication.
Supported by National Natural Science Foundation of China, No. 81770776 and No. 81973378; Cultivate Scientific Research Excellence Programs of Higher Education Institutions in Shanxi, No. 2019KJ022; and Special Project for Transformation and Guidance of Scientific and Technological Achievements in Shanxi Province, No. 201804D131044.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the First Hospital of Shanxi Medical University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yun-Feng Liu, PhD, Chief Physician, Professor, Department of Endocrinology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan 030001, Shanxi Province, China. nectarliu@163.com
Received: June 27, 2020
Peer-review started: June 27, 2020
First decision: September 18, 2020
Revised: October 9, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: December 15, 2020
Processing time: 168 Days and 14.7 Hours
Abstract
BACKGROUND

Multiple studies demonstrate that fluctuating blood glucose level produces greater damage compared with sustained hyperglycemia. Flash glucose monitoring system is an effective method in documenting blood glucose variability, contributing to better glucose management and reduced hypoglycemic event occurrence.

AIM

To investigate the improvement in glycemic variability (GV), blood glucose level, and metabolic indexes of patients with type 2 diabetes mellitus after combined treatment of exenatide once weekly (EXQW) and metformin.

METHODS

Twenty-five patients with type 2 diabetes mellitus suffering from poor blood glucose control under metformin treatment were recruited. The recruited patients were prescribed with oral metformin only (maintaining a dosage of metformin at ≥ 1500 mg/day) for 2 wk (screening period), and then given EXQW (2 mg, subcutaneous injection) for 12 wk (experimental period). The flash glucose monitoring system was used to document blood glucose values during the screening period and the last 2 wk of the experimental period.

RESULTS

Four patients were excluded for various reasons, yielding a total of 21 patients, including 17 males and 4 females, with an average age of 48.8 years, who completed this study. The estimated glycated hemoglobin, mean blood glucose, fasting and postprandial blood glucose levels, and percentage of blood glucose above 7.8 mmol/L decreased compared to those at baseline (P = 0.003, 0.003, 0.008, 0.010, 0.014, 0.017, and 0.005, respectively), while the percentage of blood glucose between 3.9 and 7.8 mmol/L significantly increased (P = 0.005). Parameters of GV including standard deviation of blood glucose, mean amplitude of glycemic excursions, mean of daily difference, area under the curve difference between percentiles 25 and 75, and area under the curve difference between percentiles 10 and 90 were significantly lower compared to that of baseline (P = 0.017, 0.006, 0.000, 0.024, 0.036, respectively). The durations of blood glucose below 3.9 mmol/L during the day and nocturnal periods significantly increased after treatment (P = 0.041 and 0.028, respectively), but there was no significant increase in severe hypoglycemia (< 3.0 mmol/L) compared with that at baseline (P = 0.207). In addition, some metabolic indicators improved after EXQW treatment.

CONCLUSION

EXQW combined with metformin can effectively improve blood glucose levels, reduce GV, and improve metabolic indicators. However, there is still a risk of nocturnal hypoglycemia, and careful attention should be paid to patients with EXQW treatment.

Keywords: Flash glucose monitoring; Glycemic variability; Type 2 diabetes mellitus; Exenatide once weekly

Core Tip: In this study, flash glucose monitoring system was used not only to observe the hypoglycemic effect of and the improvement of glycemic variability by exenatide once weekly in combination with metformin, but also to accurately assess the specific time period for the improvement of blood glucose and the time when the occurrence of hypoglycemia was concentrated. The results indicated that the combination of these drugs significantly improved fasting blood glucose, but the risk of increasing hypoglycemia, especially at night, should be cautioned.