Bempedoic acid does not increase risk of glycemia or new onset diabetes

CLEAR Outcomes analysis by glycemic status

Presented at the ESC Congress 2023 by: Kausik Ray, MD - London, UK

Introduction and methods

Patients with diabetes and CVD have greater absolute benefits with the addition of ezetimibe and PCSK9 mAbs to statin therapy. Unfortunately, many patients are unable to tolerate statins or maximize statin dose resulting in a high residual CV risk in there patients. Moreover, statins dose-dependently increase the risk of new-onset diabetes (NOD). An on-target effect of HMGCoA inhibition on NOD has been suggested by genetic research, as well as for NPC1L1 (the target of ezetimibe) and PCSK9 (the target for PCSK9 inhibitors), although no increased risk of NOD was seen in trials with ezetimibe and PCSK9 inhibitors.

Genetic studies suggest that lowering ACLY (the target of bempedoic acid) reduces CVD without increasing the risk of NOD.

A prespecified analysis of data of the CLEAR Outcomes trial was performed, investigating the efficacy of bempedoic acid compared with placebo by glycemic status (normoglycemic, prediabetes and diabetes).

In the CLEAR Outcomes trial, patients with or at high risk of CVD who were unable or unwilling to take statins were enrolled.

The efficacy outcomes in the CLEAR Outcomes and in this prespecified analysis were MACE-4 (CV death, non-fatal MI, non-fatal stroke or coronary revascularization) and MACE-3 (CV death, non-fatal MI or non-fatal stroke). Other clinical outcomes of interest were HbA1c at 1 year, fasting glucose at 1 year, NOD at the end of study. Median follow-up was 40.6 months.

Main results

• Similar reductions in LDL-c and non-HDL-c were observed with bempedoic acid at 6 months across the 3 glycemic strata.
• Bempedoic acid treatment resulted in similar benefits of MACE-4 across glycemic strata, but absolute benefit was greater in patients with diabetes.
• Similar results were observed for MACE-3.
• In patients without diabetes, bempedoic acid did not worsen HbA1 or glucose levels.
• Bempedoic acid did not increase the risk of NOD.
• In patients without diabetes, there was a modest weight loss of ~4 kg with bempedoic acid.

Conclusion

This pre-specified analysis of CLEAR Outcomes showed that in patients with diabetes who were unwilling or unable to take statins, bempedoic acid as monotherapy reduced CV risk with large absolute benefit. Moreover, treatment with bempedoic acid did not results in adverse effects on measures of glycemia or NOD in patients without diabetes at baseline.

- Our reporting is based on the information provided at the ESC Congress 2023 -

Watch a video by Kausik Ray on this study