Ezetimibe Does Not Increase Fasting Glucose Levels More than Statins Alone in Non-diabetic, Hypercholesterolemic Patients

Abstract

Lead Author’s Financial Disclosures: Dr. Toth has served on the speakers bureau for Abbvie, Amarin, AstraZeneca, Merck, Kowa, and is a consultant to Amgen, AstraZeneca, Genzyme, Kowa, and Merck. Study Funding: None Background/Synopsis: Statin therapy can be associated with a slightly increased risk of diabetes mellitus and insulin-resistance in non-diabetic patients. In prior studies, ezetimibe coadministered with statins did not increase fasting serum glucose (FSG) levels beyond those observed with statins alone in statin-na€ive, non-diabetic, hypercholesterolemic patients, up to 96 weeks in duration. Objective/Purpose: This analysis assessed the effects of ezetimibe on FSG changes when given to nondiabetic, hypercholesterolemic patients already on stable statin therapy. Methods: Data were pooled from two randomized, double-blind, eight-week, add-on‡ studies (ezetimibe [n51506] vs placebo [n5851] added to stable statin therapy) in non-diabetic patients at baseline. Mean FSG changes from baseline were estimated for each treatment group using a longitudinal data analysis model with terms for treatment and trial, and between-treatment differences were calculated. Numbers of patients with FSG $126 mg/ dL and baseline cofactor effects were also assessed. Results: No significant FSG increases from baseline were observed with statin and ezetimibe+statin in add-on studies; the between-treatment difference was also non-significant (p.0.05; see Figure). The lack of an ezetimibe effect on FSG is consistent with prior findings in statin-na€ive subjects comparing ezetimibe+statins vs statins. FSG changes were not related to age, and baseline BMI, HDL-C and TG, nor to changes from baseline in LDL-C, BMI, HDL-C, TG and ApoB. Proportions of patients with FSG $126 mg/dL during the trial were low, similar for both treatments, and highest in those with baseline FSG $100 #126 mg/dL. Conclusions: In hypercholesterolemic patients on statin therapy, addition of ezetimibe did not increase FSG levels more than statin therapy, consistent with the effects of ezetimibe+statins in statin-na€ive patients.