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

Dec 12, 2024Current medical research and opinion

Glucagon-like peptide 1 receptor agonists slightly lower LDL and total cholesterol levels regardless of weight loss: a meta-analysis of placebo-controlled trials

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Abstract

GLP-1 receptor agonists resulted in a modest 2.93 mg/dl reduction in low-density lipoprotein cholesterol (LDL-C).

The treatment consistently lowered LDL-C across different durations, with a greater reduction observed in studies lasting 12 weeks or less (5.39 mg/dl).
GLP-1 receptor agonists also reduced total cholesterol (TC) by approximately 7 mg/dl.
No significant changes were observed in triglycerides or very low-density lipoprotein cholesterol (VLDL-C).
There was no increase in high-density lipoprotein cholesterol (HDL-C) levels following treatment.
Weight change did not appear to influence the levels of LDL-C or TC.

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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 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.

RESULTS: GLP-1RAs modestly reduced LDL-C (MD -2.93, 95% CI (-5.01, -0.85), = 0.01), consistent across treatment durations: ≤12 weeks (MD: -5.39, 95% CI (-10.36, -0.42), = 0.03) and >12 weeks (MD: -2.39, 95% CI (-4.70, -0.007), = 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), = 0.07) or VLDL-C (MD = -3.99, 95%, CI (-8.73, 0.75), = 0.10). GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49), = 0.69). Weight change did not influence LDL-C (tau2 = 28.38, I2 = 99.83, R2 = 0.0, = 0.67) or TC (tau2 = 93.6, I2 = 99.86, R2 = 0.0, = 0.92). p p p p p p p p

CONCLUSION: GLP-1RA treatment modestly decreased LDL-C and TC but did not significantly affect triglycerides, VLDL-C, or HDL-C.

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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

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