Exenatide once weekly improved 24‐hour glucose control and reduced glycaemic variability in metformin‐treated participants with type 2 diabetes: a randomized, placebo‐controlled trial

Abstract

AimTo assess the effects of once‐weekly exenatide on 24‐hour glucose control and variability.Materials and methodsThis double‐blind, placebo‐controlled trial randomized metformin‐treated adults with type 2 diabetes to once‐weekly exenatide 2.0 mg or placebo. Continuous glucose monitoring (CGM) was performed at baseline and weeks 4 and 10. The primary outcome was change in CGM‐measured 24‐hour mean glucose level.ResultsIn the once‐weekly exenatide (n = 60) and placebo (n = 56) groups (modified intention‐to‐treat population), the baseline glycated haemoglobin (HbA1c) concentrations were 8.2% and 8.0%, respectively, and the fasting plasma glucose (FPG) concentration was 9.86 and 9.32 mmol/L, respectively. Once‐weekly exenatide significantly (p < 0.001) reduced 24‐hour mean glucose level versus placebo (week 4, −1.44 vs −0.29 mmol/L; week 10, −1.71 vs −0.17 mmol/L), with consistent control throughout the week. Once‐weekly exenatide significantly reduced FPG and 2‐hour postprandial glucose (PPG) levels versus placebo at week 4 (FPG, −1.65 vs −0.11 mmol/L; PPG, −1.79 vs −0.11 mmol/L) and week 10 (FPG, −2.32 vs −0.28 mmol/L; PPG, −2.46 vs −0.33 mmol/L). At week 10, once‐weekly exenatide reduced the mean amplitude of glucose excursions (MAGE; −0.84 vs 0.16 mmol/L) and standard deviation (s.d.) of mean glucose (−0.35 vs 0.04 mmol/L). By week 10, once‐weekly exenatide‐treated participants spent more time in euglycaemia (once‐weekly exenatide, 77% vs placebo, 58%), less time in hyperglycaemia (22% vs 42%), and a similar time in hypoglycaemia (0.7% vs 0.3%). Common adverse events were injection‐site nodule (once‐weekly exenatide, 10.0% vs placebo, 0.0%), urinary tract infection (6.7% vs 8.9%) and nausea (6.7% vs 0.0%).ConclusionsIn metformin‐treated participants with type 2 diabetes, once‐weekly exenatide significantly improved daily glucose control and reduced glycaemic variability at weeks 4 and 10, as shown by reductions in 24‐hour glucose, FPG and PPG levels, MAGE and s.d., and increased time spent in euglycaemia.

Minimizing Glycemic Fluctuations in Patients with Type 2 Diabetes: Approaches and Importance

“…In a recent, randomized, double-blind study, patients with T2D treated with exenatide once weekly (QW) and metformin ( n = 60) had improvements in daily glycemic control and reductions in glucose fluctuations compared with patients treated with placebo and metformin ( n = 56). 50 Exenatide QW was associated with reductions from baseline in 24-h glucose profiles at weeks 4 and 10, whereas changes with placebo were less pronounced ( Fig. 1 ).…”

Glycemic variability in newly diagnosed diabetic cats treated with the glucagon‐like peptide‐1 analogue exenatide extended release

“…11 In humans with type 2 DM, administration of the long-acting GLP-1 analogue exenatide extended release (EER) and metformin significantly improves GV compared to metformin alone. 12 Furthermore, the use of a GLP-1 analogue on a background treatment of metformin and basal insulin therapy might have a greater effect in reducing GV than prandial insulin. 13 In cats, GV has just started to be explored.…”

A Pilot Randomized-Controlled Trial on the Effect of CPAP Treatment on Glycemic Control in Gestational Diabetes: Study Design and Methods

“…Moreover, since HbA1c reflects glycemia over several weeks, potentially important changes in glucose levels over a shorter period of time, as may occur during pregnancy, may be missed. CGM has been recently used in clinical trials in patients with T2DM to more specifically characterize the effect of newer therapies on various aspects of glucose control ( 79 , 80 ). Of note, maintaining normal glucose levels with 24-h monitoring in GDM has been shown to result in improved maternal and fetal outcomes ( 81 ).…”