title: Once-weekly exenatide versus once- or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas.
abstract: OBJECTIVE
  This multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin (with or without sulfonylureas).
  
  
  METHODS
  Patients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose ≤5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C ≤7.0% and weight loss ≥1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability.
  
  
  RESULTS
  Of 216 patients (intent-to-treat population), 111 received EQW and 105 received detemir. Overall, 44.1% (95% CI, 34.7-53.9) of EQW-treated patients compared with 11.4% (6.0-19.1) of detemir-treated patients achieved the primary outcome (P < 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir in A1C (least-square mean ± SE, -1.30 ± 0.08% vs. -0.88 ± 0.08%; P < 0.0001) and weight (-2.7 ± 0.3 kg vs. +0.8 ± 0.4 kg; P < 0.0001). Gastrointestinal-related and injection site-related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group).
  
  
  CONCLUSIONS
  Treatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. melanie.davies@uhl-tr.nhs.uk
authors.forename: Melanie
authors.initials: M
authors.lastname: Davies
authors.forename: Simon
authors.initials: S
authors.lastname: Heller
authors.forename: Seamus
authors.initials: S
authors.lastname: Sreenan
authors.forename: Hélène
authors.initials: H
authors.lastname: Sapin
authors.forename: Omolara
authors.initials: O
authors.lastname: Adetunji
authors.forename: Arash
authors.initials: A
authors.lastname: Tahbaz
authors.forename: Jiten
authors.initials: J
authors.lastname: Vora
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms; D000069057:Insulin Detemir; D008687:Metformin; D000077270:Exenatide