8753 Efficacy and safety of bempedoic acid for patients with type 2 diabetes and hypercholesterolemia: a meta-analysis of randomized trials and post-hoc studies

Abstract

Abstract Disclosure: A. Godoi: None. C.H. Silva: None. L.C. Hespanhol: None. P. Romeiro: None. C. Silva: None. C.A. Balieiro: None. T. Texeira: None. Background: Statins, the primary treatment for lowering LDL cholesterol and cardiovascular risk, have been associated with a worsened glycemic control. Moreover, several patients with hypercholesterolemia, including those with type 2 diabetes mellitus (T2DM), are unable to meet treatment goals with statins. Bempedoic acid (BA) has shown promising results in trials with patients with high cholesterol and cardiovascular disease, however, its efficacy in a population restricted to patients with T2DM remains unclear. Purpose: To perform a systematic review and meta-analysis comparing the therapeutic efficacy and safety of BA versus placebo in patients with T2DM and hypercholesterolemia. Methods: PubMed, Cochrane Central and Embase were systematically searched up to January 2024 include randomized controlled studies (RCTs) and post-hoc studies assessing the use of BA in a population of patients with T2DM on prior lipid-lowering therapy. Efficacy outcomes assessed were mean change in low-density lipoprotein C (LDL-C), high-density lipoprotein C (HDL-C), and non-HDL, as well as an increase in HbA1c. Safety outcomes included incidence of hyperglycemia, gout, myalgia and treatment discontinuation due to adverse events. Outcomes were pooled using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). Statistical analysis was performed with RevMan 5.4.1 and R Studio software. Heterogeneity was assessed with I² statistics. The protocol was registered in PROSPERO. Results: A total of seven RCTs with 7475 patients with T2DM were included, of whom 3842 (51.4%) were allocated to use BA and 3633 (48.6%) were allocated to placebo. Follow-up time ranged from 2 to 52 weeks. The use of BA was associated with a significantly lower LDL-C (MD -30.19mg/dL; -37.56 to -22.82 95% CI; p<0.001), and non-HDL (MD -20.05mg/dL; -20.15 to -19.95 95% CI; p<0.001), although with a lower HDL-C (MD -5.00mg/dL; -5.01 to -4.99 95% CI; p<0.001) compared to placebo. Furthermore, BA use results in significantly lower rates of myalgia (RR 0.74; 0.60 to 0.91 95%CI; p=0.004). There were no differences regarding HbA1c increase (p=0.13), treatment discontinuation (p=0.51), hyperglycemia (p-0.57), or gout (p=0.05) between groups. Conclusion: In this meta-analysis of randomized trials and post-hoc studies, the use of BA was associated with an improved lipid profile without worsening glycemic control or causing significant adverse events, although at the cost of a lower HDL-C. Presentation: 6/1/2024