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Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-2307-8036
Article

Therapy Combining Glucagon-Like Peptide-1 Receptor Agonist with Sodium-Glucose Cotransporter 2 Inhibitor Suppresses Atherosclerosis in Diabetic ApoE-Deficient Mice

Masahiro Takubo
1   Division of Diabetes and Metabolism, Nihon University School of Medicine, 173-8610, Tokyo, Japan
,
Kentaro Watanabe
1   Division of Diabetes and Metabolism, Nihon University School of Medicine, 173-8610, Tokyo, Japan
,
Hitoki Saito
1   Division of Diabetes and Metabolism, Nihon University School of Medicine, 173-8610, Tokyo, Japan
,
Genta Kohno
1   Division of Diabetes and Metabolism, Nihon University School of Medicine, 173-8610, Tokyo, Japan
,
Hisamitsu Ishihara
1   Division of Diabetes and Metabolism, Nihon University School of Medicine, 173-8610, Tokyo, Japan
› Institutsangaben Funding This research was supported by Grants-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan (to KW: 23K06857) and by a grant from the Japan Association for Diabetes Education and Care to HI.
Funding Information Grants-in-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan — 23K06857 The Japan Association for Diabetes Education and Care —
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Abstract

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have beneficial effects on cardiovascular disease in addition to their glucose-lowering effects. In this study, the effects of these drugs, when used individually or in combination, on cardiovascular atherosclerotic lesion development were compared in diabetic ApoE-deficient (ApoE KO) hyperlipidemic mice.

Methods ApoE-KO mice were treated with streptozotocin and nicotinamide, generating a type 2 diabetes model. The mice were randomly divided into four groups: vehicle-treated (untreated), liraglutide (LIRA), ipragliflozin (IPRA), and combination therapy (combo). These mice, as well as non-diabetic controls, were fed a high-fat diet. After 8 weeks of drug administration, the heart and aorta were removed and analyzed.

Results Atherosclerotic lesions evaluated by oil red O (ORO) staining were significantly larger in the untreated group (13.4±0.8% of the total aortic area) than in the non-diabetic controls (4.4±0.5%, p<0.01), while being reduced in the combo group (6.0±1.0%, p<0.01) as compared with the untreated group. The ORO stain-positive area in the LIRA and IPRA groups tended to be reduced but their differences were not statistically significant. Transcript levels of Mcp1 and Sirt1 were significantly reduced and increased, respectively, in the combo compared with the untreated group, while no significant changes were observed in the monotherapy groups.

Conclusions The data suggest that combination therapy with liraglutide and ipragliflozin may be an efficient regimen for preventing the development of atherosclerosis in diabetic mice deficient in ApoE.

Keywords

atherosclerosis - SGLT2i - GLP-1RA

Supplementary Material



Publikationsverlauf

Eingereicht: 29. Dezember 2023
Eingereicht: 09. April 2024

Angenommen: 16. April 2024

Accepted Manuscript online:
16. April 2024

Artikel online veröffentlicht:
29. Mai 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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