The Emerging Role of Dual GLP-1 and GIP Receptor Agonists in Glycemic Management and Cardiovascular Risk Reduction

Figures & data

Figure 1 A diagrammatic depiction of the incretin effect. Reprinted from Thompson A, Kanamarlapudi V. Type 2 Diabetes Mellitus and Glucagon Like Peptide-1 Receptor Signalling. Clin Exp Pharmacol. 2013;3:4. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.⁶²

Figure 2 Pleiotropic actions of glucagon-like polypeptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in type 2 diabetes. Reprinted from Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410–421. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.²⁵ intended).

Table 1 Cardiovascular Effects of GIP in Animal Models

Animal Model		GIPR Activation	GIPR Inhibition
Atherosclerosis	ApoE knockout mice	↓Plaque formation ↓Macrophage foam cell formation ↑Plaque stability
	ApoE knockout mice with diabetes	↓Plaque formation ↓Macrophage foam cell formation
Restenosis	Femoral artery wire injury (male C57BL/6 mice)	↓Neointimal formation ↑endothelial regeneration	↑Neointimal formation
	Femoral artery wire injury with diabetes (male db/db mice)	↓Neointimal formation
Cardiac remodeling	Angiotensin II infusion (male C57BL/6-background ApoE knockout mice)	↓Cardiomyocyte enlargement ↓interstitial fibrosis
	Coronary artery ligation (male C57BL/6-background mice)	↑Scar formation	↓Mortality ↓Scar formation
	Transverse aortic constriction (male C57BL/6-background mice)		→Left ventricular function
	Doxorubicin injection (male C57BL/6-background mice)		↓Cardiac atrophy → Mortality
Inflammation	Standard diet (C57BL/6 and db misty mice)	↓Adipose tissue inflammation ↑Adipose tissue inflammation
	High fat diet	↓Adipose tissue inflammation ↑Adipose tissue expression and blood levels of adiponectin	↑Blood and adipose tissue levels of IL-6
	Diabetes (male db/db mice)	↑Adipose tissue inflammation
	Gingivitis (C57BL/6-background mice)		↑Gingival inflammation
	Endotoxemia (C57BL/6 mice)	↓ Blood IL-6 level

Notes: Arrows: ↑, increase; →, no change; ↓ decrease. Adapted from Mori Y, Matsui T, Hirano T, Yamagishi SI. GIP as a potential therapeutic target for atherosclerotic cardiovascular disease-a systematic review. Int J Mol Sci. 2020;21(4):1509. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.³²

Figure 3 Diagrammatic relationship between GIP and atherosclerosis. Reprinted from Mori Y, Matsui T, Hirano T, Yamagishi SI. GIP as a potential therapeutic target for atherosclerotic cardiovascular disease-a systematic review. Int J Mol Sci. 2020;21(4):1509. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.³²

Thompson A, Kanamarlapudi V. Type 2 Diabetes Mellitus and Glucagon Like Peptide-1 Receptor Signalling. Clin Exp Pharmacol. 2013;3:4.

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Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410–421. doi:10.1016/j.tem.2020.02.006

 PubMed Web of Science ®Google Scholar

Mori Y, Matsui T, Hirano T, Yamagishi SI. GIP as a potential therapeutic target for atherosclerotic cardiovascular disease-a systematic review. Int J Mol Sci. 2020;21(4):1509. doi:10.3390/ijms21041509

 Web of Science ®Google Scholar