Hormonal
Combined GIPR/GLP1R agonism significantly attenuates atherosclerosis severity (shifting lesions from severe to mild) in APOE*3-Leiden.CETP mice, an effect not achieved by single GIPR or GLP1R agonism.
This pre-clinical study suggests that combining GIP and GLP-1 receptor agonism may offer superior protection against atherosclerosis severity compared to using either hormone alone. For humans, this supports the development and use of dual-agonist therapies (like tirzepatide) for cardiovascular risk reduction, particularly in those with obesity and dyslipidemia, though clinical confirmation is required.
Combined GIPR/GLP1R agonism attenuated the development of severe atherosclerotic lesions, while single treatments only showed non-significant improvements... Strikingly, the non-significantly reduced atherosclerotic lesion size upon combined GIPR/GLP1R agonism was accompanied by significantly attenuated atherosclerotic lesion severity as evidenced by a shift in the distribution of severe and mild lesions... to more mild than severe lesions (37% severe vs. 63% mild lesions) upon combined treatment
Why this rating
High-quality mechanistic data in a validated human-relevant mouse model, but results are pre-clinical and not directly translatable to human efficacy without clinical trials.
Source
Combined glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonism attenuates atherosclerosis severity in APOE*3-Leiden.CETP mice
Robin van Eenige et al. · Atherosclerosis · 2023
DOI 10.1016/j.atherosclerosis.2023.03.016
More from this paper
- Combined GIPR/GLP1R agonism lowers plasma triglyceride levels by increasing VLDL turnover (reduced hepatic VLDL-TG production and increased uptake by adipose tissue and liver).Moderate
- Combined GIPR/GLP1R agonism reduces systemic low-grade inflammation, evidenced by lower hepatic inflammatory markers and circulating adhesion molecules (ICAM-1, VCAM-1).Moderate
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