title: Colesevelam plus rosuvastatin 5 mg/day versus rosuvastatin 10 mg/day alone on markers of insulin resistance in patients with hypercholesterolemia and impaired fasting glucose.
abstract: BACKGROUND
  Statin use has been associated with adverse effects on insulin sensitivity and the development of new-onset diabetes. Colesevelam exhibits favorable effects on glucose metabolism. It is not known whether the combination of colesevelam plus low-dose statin has different effects on insulin resistance versus higher-dose statin in patients with impaired fasting glucose (IFG) and hypercholesterolemia.
  
  
  METHODS
  This was a prospective randomized open-label blinded end point (PROBE) study. Forty patients with hypercholesterolemia and IFG were randomized to receive rosuvastatin 5 mg/day plus colesevelam 3.75 g/day (RC, n=20) or rosuvastatin 10 mg (R, n=20) for 3 months. The primary end point was the difference in the change of homeostasis model assessment of insulin resistance (HOMA-IR) index between the groups.
  
  
  RESULTS
  HOMA-IR index significantly decreased in the RC group (-32%, P=0.04 vs. baseline) but nonsignificantly increased (+15%, P=NS) in the R group. Insulin levels decreased in the RC group (-26%, P=NS) but increased in the R group (+15%, P=NS). Both changes in HOMA-IR and insulin differed significantly between groups (both p<0.05). Glucose levels decreased in the RC group (-5%, P=NS), whereas they remained unaltered in the R group. Similar reductions in low-density lipoprotein cholesterol were observed in both groups (-45%; P<0.001 vs. baseline). Triglycerides remained unchanged in the RC group but decreased in the R group (-24%, P<0.001 vs. baseline and P=0.02 vs. RC group).
  
  
  CONCLUSIONS
  The combination of colesevelam with rosuvastatin 5 mg/day may be associated with favorable effects on markers of insulin resistance compared with rosuvastatin 10 mg/day in patients with hypercholesterolemia and IFG. Whether this is associated with less new-onset diabetes remains unknown.
authors.affiliation: Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece.
authors.forename: Matilda
authors.initials: M
authors.lastname: Florentin
authors.forename: Evangelos N
authors.initials: EN
authors.lastname: Liberopoulos
authors.forename: Christos V
authors.initials: CV
authors.lastname: Rizos
authors.forename: Anastazia A
authors.initials: AA
authors.lastname: Kei
authors.forename: George
authors.initials: G
authors.lastname: Liamis
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kostapanos
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
mesh_terms: D000368:Aged; D000499:Allylamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D000069472:Colesevelam Hydrochloride; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005215:Fasting / Q000097:blood; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D001786:Blood Glucose; D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; D000499:Allylamine; D000068718:Rosuvastatin Calcium; D000069472:Colesevelam Hydrochloride