Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients

Xiang, Boyang; Zhao, Xuesong; Zhou, Xiang

doi:10.1186/s12933-021-01266-x

Cited by 15 publications

(8 citation statements)

References 151 publications

(189 reference statements)

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“…In meta-analyses of clinical trials in T2DM, three types of SGLT2i, including canagliflozin (Cana), dapagliflozin (Dapa), and empagliflozin (Empa) could reduce fasting plasma glucose and hemoglobin A1c (HbA1c) ( Liakos et al, 2014 ; Sun et al, 2014 ; Yang et al, 2014 ). Moreover, it has been reported that several SGLT2i showed notable beneficial effects on CVD unlike other classes of antidiabetic medications ( Dziuba et al, 2014 ; Lee et al, 2018 ; Jiang et al, 2021 ; Tan et al, 2021 ; Xiang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease

Wang

Liu

et al. 2022

Front. Pharmacol.

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Type 2 diabetes mellitus (T2DM) is associated with cardiovascular disease (CVD) and sodium glucose cotransporter 2 inhibitors, as oral medications for T2DM treatment have shown the potential to improve vascular dysfunction. The aim of this study was to evaluate the ability of canagliflozin (Cana) to relieve CVD in T2DM mice and its possible action mechanism. Mice with diabetic CVD was conducted by a high-fat diet for 24 weeks, followed by oral gavaging with metformin (200 mg/kg/day) or Cana (50 mg/kg/day) for 6 weeks. The result demonstrated that Cana reduced serum lipid accumulation, and decreased the arteriosclerosis index and atherogenic index of plasma. In addition, Cana treatment reduced the circulating markers of inflammation. More importantly, Cana improved cardiac mitochondrial homeostasis and relieved oxidative stress. Moreover, Cana treatment alleviated the myocardial injury with decreasing levels of serous soluble cluster of differentiation 40 ligand and cardiac troponin I. Thus, cardiovascular abnormality was relieved by suppressing fibrosis and basement membrane thickening, while elevating the cluster of differentiation 31 expression level. Importantly, Cana increased the ratio of gut bacteria Firmicutes/Bacteroidetes and the relative abundance of Alistipes, Olsenella, and Alloprevotella, while it decreased the abundance of Mucispirillum, Helicobacter, and Proteobacteria at various taxonomic levels in mice with diabetic CVD. In short, Cana treatment altered the colonic microbiota composition close to the normal level, which was related with blood lipid, inflammation, and oxidative stress, and might play a vital role in CVD. In general, the improvements in the gut microbiota and myocardial mitochondrial homeostasis may represent the mechanism of Cana on CVD treatment.

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Section: Introductionmentioning

confidence: 99%

Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease

Wang

Liu

et al. 2022

Front. Pharmacol.

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“…SGLT2 inhibitors have been developed based on the anti-diabetic action initiated by inhibiting renal glucose reabsorption thereby increasing urinary glucose excretion [11]. As demonstrated by several largescale clinical trials, SGLT2 inhibitors are now recognised to be capable of altering a range of metabolic and biochemical parameters thereby exerting cardio-renal protection in diabetic and non-diabetic individuals [12,13].…”

Section: Introductionmentioning

confidence: 99%

Determining the Role of SGLT2 Inhibition with Dapagliflozin in the Development of Diabetic Retinopathy

Herat¹,

Matthews²,

Ong³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Diabetic retinopathy (DR) is a major cause of blindness globally. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have been demonstrated to exert cardiorenal protection in patients with diabetes. However, their potential beneficial effect on DR is less well studied. The aim of the present study was to determine the effects of the SGLT2 inhibition with Dapagliflozin (DAPA) on DR in well-characterised DR mouse models and controls. Methods: Dapagliflozin was administered to mice with and without diabetes for 8 weeks via their drinking water at 25 mg/kg/day. Urine glucose levels were measured weekly and their response to glucose was tested at week 7. After 8 weeks of treatment, eye tissue was harvested under terminal anaesthesia. The retinal vasculature and neural structure were assessed using immunofluorescence, immunohistochemistry and electron microscopy techniques. Results: Dapagliflozin treated DR mice exhibited metabolic benefits reflected by healthy body weight gain and pronounced glucose tolerance. Dapagliflozin reduced the development of retinal microvascular and neural abnormalities, increased the beneficial growth factor FGF21 (Fibroblast Growth Factor 21). We highlight for the first time that SGLT2 inhibition results in the upregulation of SGLT1 protein in the retina and that SGLT1 is significantly increased in the diabetic retina. Conclusions: Blockade of SGLT2 activity with DAPA may reduce retinal microvascular lesions in our novel DR mouse model. In conclusion, our data demonstrates the exciting future potential of SGLT1 and/or SGLT2 inhibition as a therapeutic for DR.

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“…In rats’ models, the block of the SGLT2 pathways by empagliflozin (SGLT2-I) reduced the inflammatory/oxidative stress in the non-infarcted myocardium and the mortality, acting by the protective modification of cardiac energy metabolism [ 24 ]. In humans, the canaglifozin (SGLT2-I) caused either a glucose-independent up-regulation of cardiac survival pathways leading to cardioprotective effects in high-risk cardiovascular patients irrespective of diabetic status [ 25 ], and reduced the inflammatory burden and myocardial size in patients with atherosclerotic plaque rupture and acute myocardial infarction [ 3 ]. Indeed, the SGLT2-I could ameliorate glucose homeostasis, lowering blood pressure, weight loss, and improving vascular and coronary function [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

Sardu

Trotta

Sasso

et al. 2023

Cardiovasc Diabetol

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Background Sodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. Methods In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. Results At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149–2.176]), macrophage grade (1.188, [CI 95%: 1.073–1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180–0.651]) were independent predictors of MACEs at 1 year of follow-up. Conclusions SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids’ deposit, and FCT in Mv-NOCS patients with T2DM.

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Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients

Cited by 15 publications

References 151 publications

Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease

Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease

Determining the Role of SGLT2 Inhibition with Dapagliflozin in the Development of Diabetic Retinopathy

SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

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