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

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. 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 performed, and outcomes were analyzed using a random-effects model to calculate weighted mean differences (MDs) 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 included total cholesterol (TC), triglycerides, high density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). Subgroup analyses and meta-regression accounted for covariates. GLP-1RAs modestly reduced LDL-C (MD −2.93, 95% CI (-5.01, −0.85), <i>p</i> = 0.01), consistent across treatment durations: ≤12 weeks (MD: −5.39, 95% CI (-10.36, −0.42), <i>p</i> = 0.03) and &gt;12 weeks (MD: −2.39, 95% CI (-4.70, −0.007), <i>p</i> = 0.04). GLP-1RA reduced TC by ∼7 mg/dl. There was no significant reduction in triglycerides (MD = −7.19, 95% CI (-15.01, 0.62), <i>p</i> = 0.07) or VLDL-C (MD = −3.99, 95%, CI (-8.73, 0.75), <i>p</i> = 0.10). GLP-1RA did not increase HDL-C (MD = −0.12, 95% CI (-0.73, 0.49), <i>p</i> = 0.69). Weight change did not influence LDL-C (tau2 = 28.38, I2 = 99.83, R2 = 0.0, <i>p</i> = 0.67) or TC (tau2 = 93.6, I2 = 99.86, R2 = 0.0, <i>p</i> = 0.92). GLP-1RA treatment modestly decreased LDL-C and TC but did not significantly affect triglycerides, VLDL-C, or HDL-C.