Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: A post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials

Aim To evaluate the effect of bempedoic acid on glycaemic and lipid variables in patients with hypercholesterolaemia. Methods A patient-level pooled analysis of four phase 3, randomized, double-blind, placebo-controlled trials evaluated changes in glycaemia, change from baseline in LDL-C, and adverse events. Patients (N = 3621) on maximally tolerated statins were randomized 2:1 to oral bempedoic acid 180 mg or placebo once daily for 12 to 52 weeks with the results analysed by baseline glycaemic status (diabetes, prediabetes, or normoglycaemia). Results The annual rate of new-onset diabetes for bempedoic acid versus placebo in patients with normoglycaemia at baseline (n = 618) was 0.3% versus 0.8%, and for patients with prediabetes at baseline (n = 1868) it was 4.7% versus 5.9%. In patients with diabetes or prediabetes, bempedoic acid significantly (P < .0001) reduced HbA1c by -0.12% and -0.06%, respectively, and did not worsen fasting glucose versus placebo. Bempedoic acid significantly and consistently lowered LDL-C levels versus placebo, regardless of baseline glycaemic status (placebo-corrected difference range, -17.2% to -29.6%; P < .001 for each stratum). The safety of bempedoic acid was comparable with placebo and similar across glycaemic strata. Conclusions Bempedoic acid significantly lowered LDL-C across glycaemic strata and did not worsen glycaemic variables or increase the incidence of new-onset diabetes versus placebo over a median follow-up of 1 year.