title: Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes.
abstract: OBJECTIVE
  To evaluate ITCA 650, a continuous subcutaneous miniature osmotic pump delivery system of exenatide versus twice-daily exenatide injections (Ex-BID) in subjects with type 2 diabetes.
  
  
  METHODS
  We conducted a randomized, two-stage, 24-week, open-label, phase 2 study in type 2 diabetes inadequately controlled with metformin. Stage I: 155 subjects were randomized to 20 or 40 μg/day of ITCA 650 or Ex-BID 5 → 10 μg. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 μg/day of ITCA 650. Change from baseline for HbA1c, weight, and fasting plasma glucose were evaluated at weeks 12 and 24.
  
  
  RESULTS
  HbA1c was significantly lower in all groups after 12 and 24 weeks. Stage I: mean change in HbA1c from a mean baseline of 7.9-8.0% was -0.98, -0.95, and -0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA1c levels ≤ 7% (P < 0.05). Stage II: significant (P < 0.05) reductions in HbA1c (≈ 1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA1c ≤ 7% at 24 weeks; respectively. Weight was reduced by 2.8-3.7 kg (P < 0.05) at 24 weeks in all except the 20 → 20 μg/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 μg/day relative to Ex-BID; and 60 μg/day had the best profile of tolerability and HbA1c lowering.
  
  
  CONCLUSIONS
  ITCA 650 significantly reduced HbA1c and weight and was well tolerated. The 20 → 60 μg/day regimen was considered the best dose for further examination in phase 3.
authors: University of California, San Diego, La Jolla, California, USA. rrhenry@vapop.ucsd.edu
authors: Robert R
authors: RR
authors: Henry
authors: Julio
authors: J
authors: Rosenstock
authors: Douglas K
authors: DK
authors: Logan
authors: Thomas R
authors: TR
authors: Alessi
authors: Kenneth
authors: K
authors: Luskey
authors: Michelle A
authors: MA
authors: Baron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D014688:Venoms / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D008687:Metformin; D000077270:Exenatide
references: Diabetes Obes Metab. 2008 Jun;10 Suppl 1:25-32
references: 18435671
references: Eur J Endocrinol. 2009 Jun;160(6):909-17
references: 19318378
references: J Clin Endocrinol Metab. 2011 May;96(5):1301-10
references: 21307137
references: Patient Prefer Adherence. 2010 Sep 07;4:313-24
references: 20859458
references: Am J Med. 2005 May;118 Suppl 5A:27S-34S
references: 15850551
references: J Fam Pract. 2009 Aug;58(8 Suppl):S25-31
references: 19679028
references: Curr Med Res Opin. 2011 Nov;27 Suppl 3:13-20
references: 21942467
references: J Diabetes Sci Technol. 2008 May;2(3):461-7
references: 19885211
references: Curr Med Res Opin. 2010 Jan;26(1):231-8
references: 19921965
references: Diabetes Care. 2005 Jan;28(1):78-83
references: 15616237
references: Diabetes Educ. 2009 Nov-Dec;35(6):1014-22
references: 19934459
references: Patient Prefer Adherence. 2010 Mar 24;4:61-8
references: 20361006
references: N Engl J Med. 2005 Aug 4;353(5):487-97
references: 16079372
references: J Behav Med. 2009 Jun;32(3):278-84
references: 19184390
references: JAMA. 2007 Jul 11;298(2):194-206
references: 17622601
references: BMC Endocr Disord. 2010 Dec 09;10:20
references: 21143938
references: Pharmacology. 2010;86(1):44-57
references: 20616619
references: BMC Endocr Disord. 2011 Apr 29;11:9
references: 21529363
references: QJM. 2007 Jun;100(6):345-50
references: 17504861
references: Int J Clin Pract. 2011 Mar;65(3):314-22
references: 21314869
references: Lancet. 2008 Oct 4;372(9645):1240-50
references: 18782641
references: Diabetes Care. 2010 Feb;33(2):240-5
references: 20103556
references: Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
references: 22187469
references: Curr Med Res Opin. 2009 Mar;25(3):777-86
references: 19203299
references: Endocr Pract. 2009 Sep-Oct;15(6):540-59
references: 19858063