title: 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: OBJECTIVE
  To assess the effects of once-weekly exenatide on 24-hour glucose control and variability.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  In 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%).
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: National Research Institute, Los Angeles, California, USA.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Frías
authors.affiliation: Palm Medical Research, Las Vegas, Nevada, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: Nakhle
authors.affiliation: Medical Affairs, AstraZeneca, Wilmington, Delaware, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Ruggles
authors.affiliation: Medical Affairs, AstraZeneca, Wilmington, Delaware, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Zhuplatov
authors.affiliation: Capital Clinical Research Center, Olympia, Washington, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Klein
authors.affiliation: Department of Biostatistics, Medpace, Cincinnati, Ohio, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Integrated Medical Development, Princeton Junction, New Jersey, USA.
authors.forename: Poul
authors.initials: P
authors.lastname: Strange
keywords: 24-hour glucose profile; continuous glucose monitoring; exenatide once weekly; glycaemic variability; type 2 diabetes