Safety and efficacy of obicetrapib in dyslipidemia: systematic review and meta-analysis

Abstract Background/Introduction Cardiovascular diseases continue to be the leading cause of morbidity and mortality worldwide and dyslipidemia is one of the most important risk factors. Obicetrapib is a newer cholesteryl ester transfer protein (CETP) inhibitor with considerable potential in the treatment of dyslipidemias. Whether used separately or in combination with statins, it has several effects on blood lipids including lowering LDL cholesterol and raising HDL cholesterol. Purpose This systematic review and meta-analysis evaluates the efficacy and safety of obicetrapib for lipid management based on randomized controlled trials (RCTs). Methods A comprehensive literature search was conducted using PubMed, Cochrane Library and ClinicalTrials.gov to identify relevant RCTs published up to 25/12/2024. The included search terms were: "obicetrapib", "TA-8995", "AMG899", "DEZ 001". Studies were included if they were randomized controlled trials (RCTs) evaluating obicetrapib in adults (≥18 years) diagnosed with hypercholesterolemia or dyslipidemia and reported at least one primary or secondary outcome. Studies were excluded if they were non-randomized clinical trials, case reports, review articles, animal studies or lacked relevant outcome data for obicetrapib monotherapy. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using Mantel-Haenzel random effects model in Review Manager 5.4. Statistical significance was set at p0.05. Results We conducted a meta-analysis of five randomized controlled trials (n = 452 patients) to evaluate the impact of obicetrapib on lipid parameters assessing both efficacy and safety outcomes. Obicetrapib therapy at 5 mg and 10 mg doses resulted in significant changes in LDL-C MD: -33.06%; 95% CI: -43.03, -32.28; p0.00001, HDL-C MD: 154.92%; 95% CI: 143.35, 166.48; p0.00001, non-HDL-C MD: -31.44%; 95% CI: -35.51, -27.36; p0.00001, Apo E MD: 40.03%; 95% CI: -29.83, 50.23; p0.00001, Apo B MD: -25.86%; 95% CI: -30.60, -21.13; p 0.00001 and Apo A MD: 54.32%; 95% CI: 47.87, 60.77; p0.00001. Changes in triglycerides MD: -4.99%; 95% CI: -11.31, 1.34; p=0.12 and VLDL MD: -5.48%; 95% CI: -13.98, 3.01; p=0.21 were not statistically significant. Safety analysis showed no significant increase in serious adverse events RR: 0.59; 95% CI: 0.13, 2.60; p=0.49 or any other adverse events RR: 0.84, 95%CI: 0.67,1.05; p=0.13, including metabolic RR: 0.75; 95% CI: 0.21, 2.69; p=0.66 and gastrointestinal RR: 1.10; 95% CI: 0.51, 2.37; p=0.81 events. Conclusion(s) Obicetrapib therapy demonstrates significant efficacy in reducing LDL-C, non-HDL-C, Apo E, Apo B and Apo A levels while increasing HDL-C in plasma. Obicetrapib was well tolerated by participants, showing no significant adverse events. Long-term randomized controlled trials (RCTs) are needed to assess its sustained cardiovascular effects.Forest plots: LDL-C, HDL-C, TG, any SAE PRISMA flow diagram & RoB assessment