title: A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin.
abstract: OBJECTIVE
  To test the hypothesis that glycaemic control achieved when switching sitagliptin to exenatide twice daily plus metformin is non-inferior to adding exenatide twice daily to sitagliptin and metformin.
  
  
  METHODS
  Patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin were randomly assigned to 20 weeks of treatment with twice-daily exenatide plus placebo and metformin (SWITCH, n = 127) or twice-daily exenatide plus sitagliptin and metformin (ADD, n = 128).
  
  
  RESULTS
  Non-inferiority (0.4% margin) of SWITCH to ADD treatment, measured by change in HbA(1c) from baseline to week 20, was not shown {between-treatment difference in least-squares mean [95% CI 3 mmol/mol (0.30%)] [0.8-5.8 (0.07-0.53)]}. A greater reduction (P = 0.012) in HbA(1c) [least-squares mean (se)] was experienced by patients in the ADD group {-7 mmol/mol [-0.68%] [0.9 (0.08)]}, compared with those in the SWITCH group {-4 mmol/mol [-0.38%] [1.0 (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group (41.7%) reached < 7.0% (< 53 mmol/mol) HbA(1c) target, compared with those in the SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater fasting serum glucose (P = 0.038) and daily mean postprandial self-monitored blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group, by week 20. Patients in both groups experienced a lower incidence of nausea and vomiting compared with previous exenatide studies.
  
  
  CONCLUSIONS
  Non-inferiority of SWITCH to ADD treatment was not supported by the results of this study. In patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin, adding exenatide provided better glycaemic control than switching to exenatide. These results are consistent with the clinical approach that adding is better than switching to another oral anti-hyperglycaemic medication.
authors.affiliation: Department of Endocrinology, Mexican Institute of Social Security, Madero, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Violante
authors.forename: J H A
authors.initials: JH
authors.lastname: Oliveira
authors.forename: K-H
authors.initials: KH
authors.lastname: Yoon
authors.forename: V A
authors.initials: VA
authors.lastname: Reed
authors.forename: M B
authors.initials: MB
authors.lastname: Yu
authors.forename: O P
authors.initials: OP
authors.lastname: Bachmann
authors.forename: J
authors.initials: J
authors.lastname: Lüdemann
authors.forename: J Y C
authors.initials: JY
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001118:Argentina / Q000453:epidemiology; D001315:Australia / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007194:India / Q000453:epidemiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology; D056910:Republic of Korea / Q000453:epidemiology; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology; D014688:Venoms / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D014688:Venoms; C517652:hemoglobin A1c protein, human