NEW ORLEANS, LA—Twelve weeks of therapy with atorvastatin 20mg significantly increased fasting plasma glucose (FPG) in patients with type 2 diabetes and combined dyslipidemia; in contrast, no significant changes were noted with pitavastatin 4mg, according to results of a posthoc analysis of a multinational Phase 3 trial presented at ACC.11, the American College of Cardiology’s 60th Annual Scientific Session.
Craig A. Sponseller, MD from Kowa Pharmaceuticals America, Inc., and colleagues conducted a retrospective analysis to examine changes in FPG with pitavastatin and atorvastatin following several studies that reported deterioration of glucose metabolism following statin administration and results of Phase 3 clinical trials that demonstrated pitavastatin 2mg and 4mg did not differ statistically from atorvastatin 10mg and 20mg in reducing LDL-C.
The multicenter, double-blind trial (NK-104-305) randomized patients with type 2 diabetes and combined dyslipidemia in a 2:1 ratio to treatment with pitavastatin 4mg or atorvastatin 20mg. Mean changes in FPG levels were assessed from baseline to the end of 12 weeks within each treatment group using paired t-test; assessments between treatments used a general linear model, adjusting for study site, baseline glucose level, duration of diabetes, age, body mass index, gender, and use of insulin, diuretics, and beta-blockers when randomized.
No significant changes in FPG were noted after 12 weeks of therapy among 269 patients treated with pitavastatin compared with baseline (mean change 2.6mg/dL, P=0.1033) while significant increases in FPG were observed among the 132 patients treated with atorvastatin (9.2mg/dL, P=0.0062).
A significantly greater change in FPG was observed in the 132 patients treated with atorvastatin than pitavastatin (P=0.0081), particularly in women with type 2 diabetes (17mg/dL [n=57] for atorvastatin vs. 3.5mg/dL [n=117] for pitavastatin; P=0.0071) compared with men (3.2mg/dL [n=75] for atorvastatin vs 2mg/dL [n=152] for pitavastatin; P=0.3872). In addition, among patients treated with atorvastatin 20mg, greater changes in FPG were observed in those who had HbA1c ≥6.5% (10.4 mg/dL vs. 3.1 mg/dL for pitavastatin), and in patients who were taking insulin. After excluding patients who changed diabetes medications or were hospitalized during the study, sensitivity analyses further supported these findings.
The investigators concluded that due to the limitations of a posthoc analysis, further studies are needed not only to confirm the findings, but to ascertain relevance to clinical outcomes.