title: Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus.
abstract: This study evaluated the effects of rosiglitazone therapy on lipids and the efficacy and safety of rosiglitazone in combination with atorvastatin in patients with type 2 diabetes mellitus. Three-hundred thirty-two patients entered an 8-week, open-label, run-in treatment phase with rosiglitazone 8 mg/day, and 243 were randomized to a 16-week, double-blinded period of continued rosiglitazone plus placebo, atorvastatin 10 mg/day, or atorvastatin 20 mg/day. With rosiglitazone alone, a modest increase in low-density lipoprotein (LDL) cholesterol (9%), a shift in LDL phenotype from dense to large buoyant subfractions (52% of patients), and an increase in total high-density lipoprotein (HDL) cholesterol levels (6%), predominantly in HDL(2) levels (13%), occurred from week 0 to week 8. When atorvastatin was added, there was a further increase in HDL(3) (5%) and expected significant reductions (p <0.0001) in LDL cholesterol (-39%), apolipoprotein B (-35%), and triglyceride levels (-27%). Glycemic control achieved with rosiglitazone alone was not adversely affected by add-on atorvastatin. The combination was well tolerated compared with placebo. To conclude, in addition to the beneficial effects of rosiglitazone on glycemic control, rosiglitazone and atorvastatin in combination achieved 2 goals: the reduction of LDL cholesterol to <100 mg/dl and the removal of small dense LDL in patients with type 2 diabetes mellitus.
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA. martin_i_freed@gsk.com
authors.forename: Martin I
authors.initials: MI
authors.lastname: Freed
authors.forename: Robert
authors.initials: R
authors.lastname: Ratner
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Kreider
authors.forename: Nandita
authors.initials: N
authors.lastname: Biswas
authors.forename: Beth R
authors.initials: BR
authors.lastname: Cohen
authors.forename: John D
authors.initials: JD
authors.lastname: Brunzell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D000069059:Atorvastatin; D001786:Blood Glucose / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009656:North America; D011758:Pyrroles / Q000627:therapeutic use*; D000077154:Rosiglitazone; D012449:Safety; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D000069059:Atorvastatin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D011758:Pyrroles; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones