title: Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH.
abstract: BACKGROUND
  Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known.
  
  
  METHODS
  This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states.
  
  
  RESULTS
  Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P < .02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline.
  
  
  CONCLUSIONS
  The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which may have deleterious consequences over time and warrants further study.
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, University of Miami Miller School of Medicine, Fla.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Goldberg
authors.affiliation: Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham School of Medicine.
authors.forename: Vera A
authors.initials: VA
authors.lastname: Bittner
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Dunbar
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, Md.
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.affiliation: Grunberger Diabetes Institute, Bloomfield Hills, Mich.
authors.forename: George
authors.initials: G
authors.lastname: Grunberger
authors.affiliation: Duke University Medical Center, Durham, NC.
authors.forename: John R
authors.initials: JR
authors.lastname: Guyton
authors.affiliation: Division of Endocrinology and Metabolism, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michaels Hospital, Toronto, Ont, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Axio Research, LLC, Seattle, Wash. Electronic address: ruthm@axioresearch.com.
authors.forename: Ruth
authors.initials: R
authors.lastname: McBride
authors.affiliation: College of Public Health & Carver College of Medicine, University of Iowa, Iowa City.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University of Utah, Salt Lake City.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Simmons
authors.affiliation: Rockwood Diabetes and Endocrinology, Spokane, Wash.
authors.forename: Carol
authors.initials: C
authors.lastname: Wysham
authors.affiliation: PPD, Wilmington, NC.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Medicine, Albany VA Medical Center, NY.
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003692:Delayed-Action Preparations; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000378:metabolism; D004359:Drug Therapy, Combination; D000069499:Ezetimibe, Simvastatin Drug Combination / Q000627:therapeutic use*; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects*
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D000069499:Ezetimibe, Simvastatin Drug Combination; D000960:Hypolipidemic Agents; D007328:Insulin; D009525:Niacin
keywords: Clinical trial; Diabetes; Extended release niacin; Glucose and insulin; Heart disease; Impaired fasting glucoses