title: Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes.
abstract: OBJECTIVE
  To evaluate whether exenatide administered before breakfast and dinner (BD) or before lunch and dinner (LD) provided similar glycemic control in Latin American patients with type 2 diabetes mellitus (T2DM) who consume a small breakfast.
  
  
  METHODS
  In this open-label, 2-arm study, patients taking metformin, sulfonylureas, and/or thiazolidinediones were randomized to exenatide before BD or before LD (5-mug exenatide for 4 weeks, then 10-microg exenatide for 8 weeks). Treatment assignment was determined by a computer-generated random sequence using an interactive response system. Patients were eligible for study inclusion if they consumed <15% of their total caloric intake at breakfast. The primary endpoint was HbA(1c) change from baseline to endpoint. Secondary endpoints included fasting serum glucose (FSG) level, 7-point SMBG profile, and safety. Clinicaltrials.gov Identifier: NCT00359879.
  
  
  RESULTS
  377 participants (55% female, age 54 +/- 10 years, weight 82 +/- 15 kg, BMI 31 +/- 4 kg/m(2), HbA(1c) 8.4 +/- 0.9%; mean +/- SD) from Brazil and Mexico were randomized to study treatment. HbA(1c) reduction with exenatide administration before BD was non-inferior to administration before LD (mean difference between (LD-BD) treatments: 0.14%; 95% CI -0.04 to 0.32%, p=0.120). Both treatments resulted in statistically significant HbA(1c) reductions at endpoint (BD -1.2% and LD -1.1%, respectively, p<0.001). In Brazil, the non-inferiority criteria were met for HbA(1c) reduction between treatment arms (-0.12%; CI -0.37 to 0.13%, p=0.344), whereas in Mexico, there was a difference favoring exenatide administration before BD (0.41%; CI 0.16 to 0.66%, p=0.002). At endpoint, there were no statistical significant differences between the BD and LD arms in mean change in FSG (0.50 mmol/L; CI -0.02 to 1.02 mmol/L, p=0.058) and daily mean change in SMBG (0.19 mmol/L; CI -0.17 to 0.54 mmol/L, p=0.295). The rates of symptomatic hypoglycemia (5.2 events/patient-year vs. 6.1 events/patient-year) and nausea (23% vs. 25%), were similar between the BD and LD arms, respectively. A limitation of the study design was that caloric intake of patients and meal times were not monitored.
  
  
  CONCLUSIONS
  In T2DM patients who consume a small breakfast, exenatide administration before breakfast or lunch resulted in significant improvement in glycemic control.
authors.affiliation: Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Forti
authors.forename: Eduardo Garcia
authors.initials: EG
authors.lastname: Garcia
authors.forename: Maria B
authors.initials: MB
authors.lastname: Yu
authors.forename: Maria C
authors.initials: MC
authors.lastname: Jimenez
authors.forename: Robert G
authors.initials: RG
authors.lastname: Brodows
authors.forename: Juliana H
authors.initials: JH
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004435:Eating; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006630:Hispanic or Latino; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms