Effect of extended-release niacin on new-onset diabetes among hyperlipidemic patients treated with ezetimibe/simvastatin in a randomized controlled trial

Abstract

Objective: To determine the effect of niacin on fasting glucose (FG) and new-onset diabetes in statin/ezetimibe-treated patients.

Research design and methods: This was a prespecified secondary analysis among 942 hyperlipidemic patients randomized to ezetimibe/simvastatin (E/S; 10/20 mg) or E/S + extended-release niacin (N; titrated to 2 g) over 64 weeks.

Results: FG levels peaked by 8-12 weeks, then declined even without antidiabetic medication. At 64 weeks, 3.5% taking E/S+N versus 2.6% taking E/S met criteria for new-onset diabetes (P = 0.66). An additional 1.4% taking E/S+N versus 0.4% taking E/S transiently met criteria for diabetes and then remitted (P = 0.46). Of 28 new-diabetes diagnoses in the E/S+N group, 25 occurred by 24 weeks. Among patients with baseline diabetes, 13.9% taking E/S+N and 11.6% taking E/S underwent antidiabetic treatment modification.

Conclusions: Increased FG and new-onset diabetes with E/S+N occurred mainly around the time of initial uptitration of N and often improved or remitted without specific treatment.

Trial registration: ClinicalTrials.gov NCT00271817.

Figures

Figure 1

Time course of new-onset diabetes and effects on FG. A: Summary of new-onset diabetes. Three pairs of bars on the left compare E/S versus E/S+N groups for patients without diabetes at baseline who developed new-onset diabetes during 0–24 weeks, 24–64 weeks, and cumulatively during 64 weeks. Two pairs of bars on the right enumerate those who developed diabetes and still met criteria for diabetes at study end or transiently met criteria for diabetes, then remitted by 64 weeks (2). Details of patients who met new-onset criteria are described in Supplementary Table 2. B: Frequency of patients who developed new-onset by treatment interval. Mean changes from baseline in FG were generated using an ANCOVA model with terms for treatment and baseline FG during 24 weeks and 24–64 weeks in the full cohort (C), in patients without diabetes at baseline (D) and with diabetes at baseline (E), and those who developed new-onset diabetes (F).