Glucagon-like peptide 1 receptor agonists modestly reduced low-density lipoprotein cholesterol and total cholesterol levels independent of weight reduction: a meta-analysis and meta-regression of placebo controlled randomized controlled trials
Frederick Berro Rivera, Marielle Nicole Cabusas Chin, Polyn Luz S Pine, Monica Marie Jadena Ruyeras, Danica Janine Cabahug Galang, Keshia Marice Gandionco, Benna Lynn Faye D. Morales, Zackaree Michael V. Climaco, Nathan Ross B. Bantayan, John Vincent Magalong, Gerard Francis Mangubat, Kenneth Ong
Abstract
Background The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components are unclear. We aim to quantify the lipid lowering effects of GLP1-RAs.Methods A comprehensive database search for placebo-controlled randomized controlled trials (RCTs) on GLP-1RA treatment was conducted until January 2023. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with weighted mean difference (MD) in milligrams per deciliter (mg/dl) and 95% confidence intervals (CIs). The primary endpoint was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary endpoints were the mean difference in total cholesterol (TC), triglycerides, high density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). Subgroup analyses and meta-regression were done to account for covariates.Results Compared to placebo, GLP-1RAs modestly reduced LDL-C (MD -2.93, 95% CI (-5.01, -0.85), P = 0.01). Treatment effect was consistent regardless of duration of treatment; 12 weeks or less MD: -5.39, 95% CI (-10.36, -0.42), P = 0.03 vs >12 weeks MD: -2.39, 95% CI (-4.70, -0.007),P = 0.04, P interaction 0.28). GLP-1RA reduced TC by ∼7 mg/dl. There was no significant reduction in triglycerides (MD = -7.19, 95% CI (-15.01, 0.62], P = 0.07) and VLDL-C ∼4 mg/dl(MD = -3.99, 95%, CI (-8.73, 0.75), P = 0.10). Furthermore, GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49], P = 0.69. Regression analysis established that mean change in weight did not affect the treatment effect on LDL-C (tau2 = 28.38, I2 = 99.83, R2 = 0.0, p = 0.67), and total cholesterol (tau2 = 93.6, I2 = 99.86, R2 = 0.0, p = 0.92).Conclusion Patients on GLP-1RA experienced modest LDL-C and TC lowering compared to placebo. GLP-1RA did not decrease triglycerides and VLDL-C. GLP-1RA did not increase HDL-C.