Author + information
- Received April 19, 2018
- Revision received September 10, 2018
- Accepted September 14, 2018
- Published online November 21, 2018.
- Günaj Rakipovski, PhDa,
- Bidda Rolin, DVMa,
- Jane Nøhr, PhDa,b,
- Ib Klewe, PhDa,c,
- Klaus S. Frederiksen, PhDa,
- Robert Augustin, PhDa,
- Jacob Hecksher-Sørensen, PhDa,d,
- Camilla Ingvorsen, PhDa,
- Joseph Polex-Wolf, PhDa and
- Lotte Bjerre Knudsen, DMSca,∗ ()
- aGlobal Research, Novo Nordisk A/S, Maaloev, Denmark
- bBiopeople, University of Copenhagen, Copenhagen, Denmark
- cDepartment of Signal Transduction, Lundbeck, Copenhagen, Denmark
- dGubra, Hørsholm, Denmark
- ↵∗Address for correspondence:
Dr. Lotte Bjerre Knudsen, Novo Nordisk, Novo Nordisk Park, DK-2760 Maaloev, Denmark.
• The GLP-1RAs liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients.
• In ApoE−/− mice and LDLr−/− mice, liraglutide and semaglutide treatment significantly attenuated plaque lesion development, in part independently of body weight and cholesterol lowering.
• Semaglutide decreased levels of plasma markers of systemic inflammation in an acute inflammation model (lipopolysaccharide), and transcriptomic analysis of aortic atherosclerotic tissue revealed that multiple inflammatory pathways were down-regulated by semaglutide.
The glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. The mode of action is suggested to occur through modified atherosclerotic progression. In this study, both of the compounds significantly attenuated plaque lesion development in apolipoprotein E-deficient (ApoE−/−) mice and low-density lipoprotein receptor-deficient (LDLr−/−) mice. This attenuation was partly independent of weight and cholesterol lowering. In aortic tissue, exposure to a Western diet alters expression of genes in pathways relevant to the pathogenesis of atherosclerosis, including leukocyte recruitment, leukocyte rolling, adhesion/extravasation, cholesterol metabolism, lipid-mediated signaling, extracellular matrix protein turnover, and plaque hemorrhage. Treatment with semaglutide significantly reversed these changes. These data suggest GLP-1RAs affect atherosclerosis through an anti-inflammatory mechanism.
All authors are or have been shareholders and/or employees of Novo Nordisk. Novo Nordisk markets liraglutide for the treatment of diabetes and obesity, and semaglutide for the treatment of diabetes.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received April 19, 2018.
- Revision received September 10, 2018.
- Accepted September 14, 2018.
- 2018 The Authors