title: Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus.
abstract: BACKGROUND
  Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤ 7.0%).
  
  
  METHODS
  1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤ 7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined.
  
  
  RESULTS
  Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47-0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤ 7.0% (OR: 0.46 (0.31-0.69), p = 0.0002).
  
  
  CONCLUSIONS
  Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, USA ; Harvard Medical School, Boston, MA, USA ; VeroScience LLC, 1334 Main Road, Tiverton, RI 02878, USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Chamarthi
authors.affiliation: Harvard Medical School, Boston, MA, USA ; Veterans Affairs Healthcare System, 1400 VFW Parkway, W Roxbury, Boston, MA 02132, USA ; Divisions of Aging, Cardiology and Preventive Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.affiliation: Ochsner Medical Center, 1514 Jefferson Hwy, New Orleans, LA 70121, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Blonde
authors.affiliation: Eastern Virginia Medical School Strelitz Diabetes Center and Neuroendocrine Unit, 855 W. Brambleton Avenue, Norfolk, VA 23510, USA.
authors.forename: Aaron
authors.identifier: 0000-0002-5279-0628
authors.initials: A
authors.lastname: Vinik
authors.affiliation: VeroScience LLC, 1334 Main Road, Tiverton, RI 02878, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Scranton
authors.affiliation: VeroScience LLC, 1334 Main Road, Tiverton, RI 02878, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ezrokhi
authors.affiliation: Everest Clinical Research Services Inc., 675 Cochrane Dr., Markham, ON, Canada L3R 0B8.
authors.forename: Dean
authors.initials: D
authors.lastname: Rutty
authors.affiliation: VeroScience LLC, 1334 Main Road, Tiverton, RI 02878, USA.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Cincotta
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001971:Bromocriptine / Q000008:administration & dosage / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D018450:Disease Progression; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D007004:Hypoglycemic Agents; D001971:Bromocriptine