title: Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit*.
abstract: OBJECTIVE
  To assess the extent, safety, efficacy and tolerability of reported off-licence exenatide use through a nationwide audit.
  
  
  METHODS
  The Association of British Clinical Diabetologists hosted a password-protected, online collection of anonymized data of exenatide use in real clinical practice. Three hundred and fifteen contributors from 126 centres across UK provided data on 6717 patients. HbA1c and weight changes, exenatide discontinuation, adverse events and treatment satisfaction were compared between non-insulin and insulin-treated patients.
  
  
  RESULTS
  Four thousand eight hundred and fifty-seven patients had baseline and follow-up treatment status with mean (±s.d.) baseline HbA1c 9.45 ± 1.69% and BMI 40.0 ± 8.2 kg/m(2) . Of the 4857 patients, 1921 (39.6%) used exenatide with insulin. Comparing patients who continued insulin with exenatide with non-insulin-treated patients, mean (±s.e.) latest HbA1c and weight reduction (median 26 weeks) were 0.51 ± 0.06 versus 0.94 ± 0.04% (p < 0.001) and 5.8 ± 0.2 versus 5.5 ± 0.1 kg (p = 0.278). Insulin-treated patients had higher rates of exenatide discontinuation (31.0 vs. 13.9%, p < 0.001), hypoglycaemia (8.9 vs. 6.1%, p < 0.001), gastrointestinal side effects (28.4 vs. 25.0%, p = 0.008) and treatment dissatisfaction (20.8 vs. 5.7%, p < 0.001). However, 34.2% of the patients continuing insulin still achieved HbA1c reduction ≥1%. There was significant insulin discontinuation, dose reduction and greater sulphonylurea discontinuation among insulin-treated patients.
  
  
  CONCLUSIONS
  Addition of exenatide to obese, insulin-treated patients can improve glycaemia and weight. Adverse events were statistically but probably not clinically significantly higher, but combination treatment was less well tolerated. Overall, exenatide was less effective in lowering HbA1c among insulin-treated patients, although significant number of insulin-treated patients still achieved significant HbA1c, weight and insulin reductions. Further research into identifying obese, insulin-treated patients who will tolerate and benefit from exenatide treatment is urgently needed.
authors.affiliation: Department of Diabetes, City Hospital, Birmingham, UK. kythong@gmail.com
authors.forename: K Y
authors.initials: KY
authors.lastname: Thong
authors.forename: B
authors.initials: B
authors.lastname: Jose
authors.forename: N
authors.initials: N
authors.lastname: Sukumar
authors.forename: M L
authors.initials: ML
authors.lastname: Cull
authors.forename: A P
authors.initials: AP
authors.lastname: Mills
authors.forename: T
authors.initials: T
authors.lastname: Sathyapalan
authors.forename: W
authors.initials: W
authors.lastname: Shafiq
authors.forename: A S
authors.initials: AS
authors.lastname: Rigby
authors.forename: C
authors.initials: C
authors.lastname: Walton
authors.forename: R E J
authors.initials: RE
authors.lastname: Ryder
mesh_terms: D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D006113:United Kingdom; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms