Effect of bempedoic acid plus ezetimibe fixed-dose combination vs ezetimibe or placebo on low-density lipoprotein cholesterol in patients with type 2 diabetes and hypercholesterolemia not treated with statins

Harold E Bays; Seth J Baum; Eliot A Brinton; Jorge Plutzky; Jeffrey C Hanselman; Rujun Teng; Christie M Ballantyne

doi:10.1016/j.ajpc.2021.100278

Effect of bempedoic acid plus ezetimibe fixed-dose combination vs ezetimibe or placebo on low-density lipoprotein cholesterol in patients with type 2 diabetes and hypercholesterolemia not treated with statins

Am J Prev Cardiol. 2021 Oct 4:8:100278. doi: 10.1016/j.ajpc.2021.100278. eCollection 2021 Dec.

Authors

Harold E Bays¹, Seth J Baum², Eliot A Brinton³, Jorge Plutzky⁴, Jeffrey C Hanselman⁵, Rujun Teng⁵, Christie M Ballantyne⁶

Affiliations

¹ Louisville Metabolic and Atherosclerosis Research Center, Inc., Louisville, KY, USA.
² Excel Medical Clinical Trials, Inc., Boca Raton, FL, USA.
³ Utah Lipid Center, Salt Lake City, UT, USA.
⁴ Brigham and Women's Hospital, Boston, MA, USA.
⁵ Esperion Therapeutics, Inc., Ann Arbor, MI, USA.
⁶ Baylor College of Medicine, Houston, TX, USA.

Abstract

Objective: Statins are sometimes associated with worsened glycemic control. Patients with type 2 diabetes mellitus (T2DM) may require non-statin therapies to achieve low-density lipoprotein cholesterol (LDL-C) lowering goals. This study evaluated the efficacy and safety of bempedoic acid 180 mg plus ezetimibe 10 mg fixed-dose combination (BA + EZE FDC) in patients with T2DM and hypercholesterolemia who were not receiving background statins or other lipid-lowering therapy.

Methods: Patients with T2DM and elevated LDL-C levels were enrolled into this phase 2, double-blind study (NCT03531905). Patients received placebo during a 5-week washout period where background lipid-lowering therapies (including statins) were discontinued. Eligible patients were then randomized 1:1:1 to receive either BA + EZE FDC, ezetimibe 10 mg, or placebo once daily for 12 weeks. Assessments included the percent change from baseline to week 12 in LDL-C, other lipid parameters, and high-sensitivity C-reactive protein (hsCRP); and the monitoring of safety and tolerability.

Results: Among 179 randomized patients, baseline characteristics following the washout period were similar across treatment groups, with mean LDL-C levels of 142.6 mg/dL and mean glycated hemoglobin of 8.0%. At week 12, BA + EZE FDC therapy lowered mean LDL-C levels by 38.8%, significantly more than ezetimibe alone (19.2%; difference, 19.5% [95% confidence interval (CI), 13.4%-25.7%]; p < 0.001) or placebo (increase of 0.9%; difference, 39.6% [95% CI, 33.4%-45.8%]; p < 0.001). BA + EZE FDC significantly reduced hsCRP levels from baseline vs ezetimibe (29.2%; p = 0.005) and vs placebo (36.7%; p < 0.001). Incidence of treatment-emergent adverse events was low in all treatment groups, with no indication of worsened glycemic control.

Conclusion: In patients with T2DM and hypercholesterolemia who were not receiving statins or other lipid-lowering drugs, BA + EZE FDC significantly lowered LDL-C levels and was generally well tolerated.

Keywords: Bempedoic acid; Diabetes mellitus type 2; Ezetimibe; Hypercholesterolemia.