Canagliflozin for Prevention of Cardiovascular and Renal Outcomes in type2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Tian, Lei; Cai, Yuzi; Zheng, Huaiping; Ai, Sinan; Zhou, Mengqi; Luo, Qian; Tang, Jingyi; Liu, Weijing; Wang, Yaoxian

doi:10.3389/fphar.2021.691878

Cited by 10 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Cana decreased serum leptin and interleukin-6 (IL-6), while it increased serum adiponectin and tumor necrosis factor alpha (TNF-alpha) in T2DM patients, which favorably impacted insulin sensitivity and CVD risk ( Garvey et al, 2018 ). Recently, several clinical studies indicated that cardiovascular events were lower after Cana treatment in T2DM patients ( Neal et al, 2017 ; Mahaffey et al, 2018 ; Perkovic et al, 2019 ; Tian et al, 2021 ). In addition, Cana significantly altered cecal microbiota composition in renal failure mice and decreased the levels of microbiota-derived uremic toxins in chronic kidney disease ( Mishima et al, 2017 ).…”

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.

View full text Add to dashboard Cite

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.

show abstract

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.

View full text Add to dashboard Cite

show abstract

“…Canagliflozin reduces ESRD risk by 30%. 30 Canagliflozin reduces cardiovascular mortality, myocardial infarction, stroke, and heart failure hospitalizations. Their findings are similar to systematic reviews and meta-analyses of SGLT2 inhibitortreated T2DM and CKD patients in randomized controlled trials.…”

Section: Discussionmentioning

confidence: 99%

“…Their findings are similar to systematic reviews and meta-analyses of SGLT2 inhibitortreated T2DM and CKD patients in randomized controlled trials. 30,31 The CREDENCE study approved canagliflozin for treating diabetic nephropathy and lowered the incidence of heart failure hospitalization in T2DM patients. CKD patients' elevated glucose load at the single nephron level keeps SGLT2 inhibitors' natriuretic and diuretic effects.…”

Section: Discussionmentioning

confidence: 99%

Use of Sodium-Glucose Transport Protein 2 (Sglt2) Inhibitors in Diabetic Kidney Disease (Dkd)

Rajagukguk

2023

JARMHS

View full text Add to dashboard Cite

SGLT2 inhibitors have emerged as a major disease-modifying therapy for preventing the development of chronic kidney disease (CKD). These agents can be used to prevent the decline in renal function through the reduction of glomerular hypertension mediated through tubuloglomerular feedback apart from their effects on glycemic control. The indications for SGLT2 inhibitors have evolved based on growing evidence from randomized controlled trials and broadly fit into five categories, including: glycemic control/metabolic risk, reduced ASCVD, heart failure, diabetic kidney disease with albuminuria, and nondiabetic CKD with albuminuria. . The initial trial was performed in patients with relatively good overall renal function, although sub-analyses suggest that the beneficial effect may extend to patients with CKD. SGLT2 inhibitors block glucose reabsorption in the renal tubules and are effective in reducing glucose levels based on the amount of glucose filtered, thereby increasing the glomerular filtration rate. The greatest transport burden on the diabetic kidney is in the early proximal tubule. SGLT2 inhibitors make the transport load more evenly distributed between the tubular segments. In addition, the total tubular transport load is reduced by lowering GFR. The SGLT2 inhibitory effect helps maintain mitochondrial function and tubular cell metabolism which can maintain tubular function and GFR in the long term.

show abstract

“…Considering the high incidence of T2DM combined with CVD, some new hypoglycemic drugs with cardiovascular protective effect have attracted extensive attention. The sodium glucose cotransporter 2 (SGLT-2i), such as dapagli ozin, canagli ozin, and empagli ozin, have demonstrated good cardiovascular safety in large-scale experimental studies on cardiovascular outcomes, especially in reducing the risk of heart failure [9][10][11]. Glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proved to be bene cial for CVD by both oral administration and subcutaneous injection [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis

Huang

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

Background In recent years, the incidence of diabetes mellitus has been increasing annually and cardiovascular complications secondary to diabetes mellitus have become the main cause of death in diabetic patients. Although some novel glucose-lowering drugs have been shown to be cardioprotective, it is unclear which glucose-lowering drugs are effective in improving cardiac remodeling and fundamentally delay the progression of heart failure. The purpose of this network meta-analysis was to compare the effects of sodium glucose cotransporter type 2 inhibitor (SGLT-2i), glucagon-like peptide 1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 inhibitor (DPP-4i) on ventricular remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods Articles published prior to 24 August 2022 were retrieved in four electronic databases: PubMed, EMBASE, Cochrane Library, and Web of Science. We included randomized controlled trials (RCTs) and a small cohort study in this meta-analysis. The differences of mean changes of left ventricular ultrasonic parameters between the treatment group and the control group were compared. Results A total of 31 RCTs and 4 cohort studies involving 4322 patients were analyzed. SGLT-2i had significantly reduced left ventricular end-diastolic diameter (LVEDD) [MD=-0.72ml, 95% CI (-1.30, -0.14)] and LV mass index (LVMI) [MD=-0.28g/m2, 95% CI (-0.43, -0.12)]. GLP-1RA had significantly reduced LV end-systolic diameter (LVESD) [MD=-0.38mm, 95% CI (-0.66, -0.10)], LVMI [MD=-1.07g/m2, 95% CI (-1.71, -0.42)], and e' [MD=-0.43cm/s 95% CI (-0.81, -0.04)]. DPP-4i significantly improved e' [MD=3.82cm/s, 95%CI (2.92,4.7)] and E/e' [MD = -5.97 95% CI (-10.35, -1.59)], but decreased LV ejection fraction (LVEF) [MD = -0.89% 95% CI (-1.76, -0.03)]. Conculusion GLP-1RA were more significantly associated with improvement in LVESD and LVMI, but significantly decreased e'. DPP-4i were more strongly associated with improvement in e' and E/e', but significantly inhibited LVEF. SGLT-2i significantly improved LVMI and LVEDD in the overall population, as well as E/e' and SBP in T2DM patients combined with CVD, without showing any negative effect on left ventricular function. Therefore, we recommend SGLT-2i as the most effective drug for reversing ventricular remodeling.

show abstract

Canagliflozin for Prevention of Cardiovascular and Renal Outcomes in type2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Cited by 10 publications

References 45 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

Use of Sodium-Glucose Transport Protein 2 (Sglt2) Inhibitors in Diabetic Kidney Disease (Dkd)

Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis

Contact Info

Product

Resources

About