Comparison of Blood Glucose Variability Between Exenatide and Biphasic Insulin Aspart 30 in Chinese Participants with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A Multicenter, Open-Label, Randomized Trial

Abstract

Introduction: To compare blood glucose variability (GV) in Chinese participants with type 2 diabetes mellitus (T2DM) whose blood glucose levels are inadequately controlled with metformin monotherapy after twice-daily exenatide or biphasic insulin aspart 30 (BIAsp30).

Methods: In this 16-week multicenter, randomized clinical trial, 104 participants were randomized 1:1 to receive exenatide (exenatide group) or BIAsp30 (BIAsp30 group) twice daily. All participants continued metformin treatment. The primary outcome was the change in GV as measured by a continuous glucose monitoring system (CGMS) from baseline to 16 weeks.

Results: At 16 weeks, both the Exenatide and BIAsp30 groups effectively decreased mean glucose (MG), but neither group changed the mean amplitude of glycemic excursion (MAGE), largest amplitude of glycemic excursion (LAGE), mean of daily difference (MODD), or standard deviation of blood glucose (SDBG). The decrease in 2-h post-breakfast glucose excursions was greater in the Exenatide group compared to the BIAsp30 group, with a least square (LS) mean difference [95% CI] of (1.58 [0.53, 2.63]). Exenatide also significantly reduced 2-h post-lunch glucose excursion compared to BIAsp30 (LS mean difference [95% CI], 1.19 [0.18, 2.20]). The Exenatide group had significantly reduced body weight and body mass index (BMI), while the BIAsp30 group had increased weight and had no change in BMI. Both treatments were well tolerated with no serious hypoglycemic events and with fewer identified hypoglycemic events in the Exenatide group than in the BIAsp30 group (5.77% vs. 17.31%, P < 0.01).

Conclusion: Although there was no difference in change of GV between Exenatide and BIAsp30, exenatide provided more improvement in postprandial glucose excursion and weight control, without increasing the risk of hypoglycemia in Chinese patients with T2DM whose blood glucose was inadequately controlled with metformin. These findings may provide new options for patients who choose further hypoglycemic treatment, especially in patients with obesity who have large postprandial plasma glucose excursions.

Trial registration: ClinicalTrials.gov indentifier: NCT02449603.

Keywords: Biphasic insulin aspart 30 (BIAsp30); Continuous glucose monitoring system (CGMS); Exenatide; Glucose variability; Postprandial glucose excursion.

Fig. 1

Flow of participants through the study. FAS full analysis set included all randomized participants receiving at least one dose of any of the trial products. PAS per protocol set, the data set was determined during a blind audit after the completion of the trial, including all cases that met the trial protocol, had good compliance, had not taken the prohibited drugs during the trial, and had completed the CRF requirements. PPS per protocol set, the population was the secondary population for efficacy evaluation in this study

Fig. 2

Efficacy comparison between Exenatide and BIAsp30 at week 16 (FAS LOCF). a Glycated hemoglobin (HbA1c) values at baseline and week 16. b Fasting plasma glucose (FPG) values at baseline and week 16. c 2-h postprandial plasma glucose values (2-h PPG) at baseline and week 16. d Weight over time, mean of actual value, SD not shown. *P < 0.05. e Hypoglycemic incidence. Total events, blood glucose level ≤ 3.9 mmol/l; severe events, hypoglycemic events requiring help from others. **P < 0.01. f Heart rate at baseline and week 16. g Serum 8-iso-PGF2α at baseline and week 16. h Serum MCP-1 at baseline and week 16