title: Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin.
abstract: OBJECTIVE
  The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin.
  
  
  METHODS
  The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo).
  
  
  RESULTS
  Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher's exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset).
  
  
  CONCLUSIONS
  B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.
authors.affiliation: a VeroScience LLC , Tiverton , RI , USA.|b Division of Endocrinology , Diabetes and Hypertension, Brigham and Women's Hospital , Boston , MA , USA.|c Department of Medicine , Harvard Medical School , Boston , MA , USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Chamarthi
authors.affiliation: a VeroScience LLC , Tiverton , RI , USA.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Cincotta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001971:Bromocriptine / Q000008:administration & dosage / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D001971:Bromocriptine; D008687:Metformin
keywords: Bromocriptine; circadian; dopamine; insulin resistance; insulin sensitizer; type 2 diabetes mellitus