Scientific reportsApr 7, 2026

Early treatment with tirzepatide or semaglutide may reduce artery plaque in mice lacking ApoE

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 8, 2026

Abstract

Tirzepatide significantly reduced aortic plaque formation in early diabetic mice compared to control.

Both tirzepatide and semaglutide suppressed aortic plaque formation in early diabetes but did not show significant effects in late diabetes or non-diabetic groups.
Both treatments modestly improved blood sugar and lipid levels in the early diabetes group.
Tirzepatide markedly reduced levels of inflammatory markers, such as Mcp-1, Il-6, I-cam, and Cd68, while semaglutide showed some overlapping effects.
Anti-inflammatory effects of tirzepatide were also observed in non-diabetic mice, indicating potential vascular protection independent of metabolic control.
Tirzepatide's anti-atherosclerotic effects are comparable to those of semaglutide, suggesting that signaling from both GIP and GLP-1 may provide vascular benefits.

Simplified

This study aimed to investigate the anti-atherosclerotic properties of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist, in comparison with semaglutide, a selective GLP-1 receptor agonist. ApoE knockout mice were divided into early diabetes (dosed from 10 to 22 weeks of age), late diabetes (dosed from 18 to 30 weeks of age), and non-diabetic groups after streptozotocin treatment, and each group received semaglutide, tirzepatide, or saline for 12 weeks. In the early diabetes group, both agents significantly suppressed aortic plaque formation compared with control, while modestly improving glycemia and lipid levels. No significant vascular effects were observed in late diabetes or non-diabetic groups. Tirzepatide markedly reduced inflammatory mediators, including Mcp-1, Il-6, I-cam, and Cd68, whereas semaglutide showed partial overlap. Notably, these anti-inflammatory effects were also detected in non-diabetic mice, suggesting vascular protection may involve arterial actions independently of metabolic control. Taken together, our findings demonstrate that tirzepatide exerts anti-atherosclerotic effects comparable to semaglutide, supporting the concept that GIP and GLP-1 signaling can confer vascular benefits. These results highlight the potential clinical relevance of dual incretin receptor agonism for cardiovascular risk reduction, although further studies are required to clarify the specific role of GIP signaling.

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Competing interests

Declarations. Competing interests: T.K. has received honoraria for lectures from Novo Nordisk Pharma and Sumitomo Pharma. S. N. has received honoraria for lectures from Novo Nordisk Pharma and Daiichi Sankyo. K.K. has served as an advisor to, received honoraria for lectures from and received scholarship grants from Novo Nordisk Pharma, Sanwa Kagaku, Taisho Pharma, Kowa, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Astellas and Boehringer Ingelheim. H.K. has received honoraria for lectures, scholarship grants and research grants from Novo Nordisk Pharma, Sanofi, Eli Lilly, Boehringer Ingelheim, Taisho Pharma, Sumitomo Pharma, Takeda Pharma, Ono Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Kissei Pharma, MSD, AstraZeneca, Astellas, Novartis, Kowa and Abbott. All other authors have no conflict of interest.

PubMed

Early treatment with tirzepatide or semaglutide may reduce artery plaque in mice lacking ApoE

Abstract

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Funding

Competing interests

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Abstract

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