title: Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia.
abstract: Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy.
authors.affiliation: CGH Medical Center, Sterling, Illinois; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: Peter.Toth@cghmc.com.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Lipid Clinic, Point Médical, Dijon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Farnier
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Joanne
authors.initials: J
authors.lastname: Foody
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Tomassini
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Erin
authors.initials: E
authors.lastname: Jensen
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Polis
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hanson
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Musliner
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tershakovec
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D015897:Comorbidity; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use*; D005215:Fasting; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000378:metabolism; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D019821:Simvastatin; D000069438:Ezetimibe