title: Onset of Glycemic and Weight Outcomes in Patients Initiating Exenatide Once Weekly: The Relationship of Exenatide Exposure with Efficacy over the First 24 Weeks of Treatment.
abstract: BACKGROUND
  Exenatide is gradually released from exenatide once weekly (QW) microspheres, and at steady state, consistently controls glycated hemoglobin (HbA1c) in patients with type 2 diabetes (T2D). This post hoc analysis examined the timing to onset of clinical responses and their correlations with exenatide concentrations after initiation of exenatide QW in patients with T2D.
  
  
  METHODS
  Trial data were retrospectively analyzed to explore the early clinical responses to exenatide QW, including the relationship of exenatide concentration with its effects on efficacy [fasting plasma glucose (FPG), HbA1c, and body weight] and tolerability (nausea and vomiting). Exenatide QW efficacy and tolerability data were from DURATION-5, a 24-week, randomized, comparator-controlled trial [intent-to-treat (ITT) population]. Exenatide concentrations were measured in a patient subset (pharmacokinetic population).
  
  
  RESULTS
  In the ITT (n = 129)/pharmacokinetic (n = 72) populations, baseline FPG, HbA1c, and body weight were 173/173 mg/dL, 8.5%/8.4%, and 97/98 kg, respectively. Exenatide concentrations gradually increased until reaching steady state at week 8. By week 4, the FPG reduction (-32.4 mg/dL) was 94% of the week 24 reduction (-34.6 mg/dL). Reductions in HbA1c began by week 4 (-0.6%) and stabilized by week 14 (week 24: -1.6%). Weight reduction at week 4 was -0.7 kg and decreased further (week 24: -2.3 kg). Peak nausea (7.2%) and vomiting (2.4%) occurred at weeks 6-8, declining thereafter.
  
  
  CONCLUSIONS
  Clinically relevant responses to exenatide QW were evident by week 4, after exenatide concentration passed the therapeutic threshold but before steady state was achieved.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00877890.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: Texas Diabetes and Endocrinology, Austin, TX, USA. tblevins@texasdiabetes.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blevins
authors.affiliation: AstraZeneca, Fort Washington, PA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ruggles
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Hardy
keywords: Body weight; Exenatide once weekly; Fasting plasma glucose; HbA1c; Nausea