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
