In 8,236 diabetes patients from ACCELERATE, evacetrapib raised HDL by 131% and lowered LDL by 32%, yet produced no clinical benefit (BMJ Open Diabetes Res Care 2020)

Original title: Effect of CETP inhibition with evacetrapib in patients with diabetes mellitus enrolled in the ACCELERATE trial

BMJ Open Diabetes Res Care · 1 March 2020 · 6

Menon V, Kumar A, Patel DR, St John J, Riesmeyer J, Weerakkody G, Ruotolo G, Wolski KE, McErlean E, Cremer PC, Nicholls SJ, Lincoff AM et al.

Among 8,236 patients with diabetes mellitus enrolled in the ACCELERATE trial (evacetrapib n = 4,127, placebo n = 4,109, median follow-up 26 months), this analysis compared time to the first cardiovascular death, myocardial infarction, stroke, revascularisation, or hospitalisation for unstable angina. From a mean baseline LDL of 80 mg/dL and HDL of 44 mg/dL, evacetrapib produced a sustained 131% mean increase in HDL and 32% mean decrease in LDL by 3 months, and haemoglobin A1c was modestly lower with evacetrapib at 6 months (7.08% versus 7.15%, p=0.023). Diabetes patients had substantially higher composite event rates than non-diabetes patients overall (15.2% versus 10.6%). Within the diabetes group, event rates did not differ significantly between evacetrapib and placebo (14.5% versus 16%, hazard ratio 0.95, 95% CI, 0.85 to 1.07, p=0.38), with no significant treatment-by-diabetes interaction. The authors conclude that despite favourable lipid and HbA1c changes, evacetrapib gave no clinical outcome benefit in this high-risk diabetic population.

Original abstract

Background: High-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL) levels. We evaluated the impact of treatment with evacetrapib versus placebo in the subset of 8236 patients with diabetes mellitus (DM) enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes trial.

Methods And Results: Time to first occurrence of any component of the primary composite endpoint of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina was compared among patients with DM randomized to treatment with evacetrapib (n=4127) or placebo (n=4109) over a median of 26 months of follow-up. The mean baseline LDL at initiation was 80 mg/dL with a mean baseline HDL of 44 mg/dL. In patients with DM, evacetrapib resulted in a 131% mean increase in HDL levels and a 32% mean decrease in LDL at 3 months that was sustained during the course of the trial. At 6 months, hemoglobin A1c (HbA1c) levels were lower with evacetrapib than placebo (7.08% vs 7.15%, p=0.023). Composite event rates were higher in patients with DM than without DM (Kaplan-Meier estimates: 15.2% vs 10.6%, HR 1.46, 95% CI 1.30 to 1.64, p<0.001). In the DM group, event rates for the composite endpoint (14.5% evacetrapib vs 16% placebo, HR 0.95, 95% CI 0.85 to 1.07, p=0.38) and individual components of the composite were similar for both evacetrapib and placebo groups. No significant treatment interaction between treatment assignment and diabetes status was noted.

Conclusion: Despite a favorable increase in HDL, and decreases in LDL and HbA1c levels in patients with DM, we observed no benefits of treatment with evacetrapib on prespecified clinical outcomes in this high-risk population.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.