A systematic review examining the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on biomarkers of inflammation and oxidative stress

Bray, Jonathan James Hyett; Foster‐Davies, Harri; Stephens, Jeffrey W.

doi:10.1016/j.diabres.2020.108368

Cited by 37 publications

(31 citation statements)

References 64 publications

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“…26,27 Sodium-glucose cotransporter-2 (SGLT2) inhibitors have similar cardiorenal protective properties and we have recently described that SGLT2 inhibitors reduce biomarkers of inflammation and oxidative stress. 28 Although a number of mechanisms have been proposed, it is unclear how GLP-1RAs exert their cardiorenal protective effects in patients with T2DM and whether an impact on inflammation and oxidative stress may contribute. This meta-analysis and systematic review of randomised trials aims to examine the effect of GLP-1RAs on inflammatory and oxidative stress biomarkers in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…The LEADER and REWIND trials also report a greater than 20% reduction in the risk of developing new macroalbuminuria, along with favourable trends in other clinically relevant adverse renal outcomes 26,27 . Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors have similar cardiorenal protective properties and we have recently described that SGLT2 inhibitors reduce biomarkers of inflammation and oxidative stress 28 . Although a number of mechanisms have been proposed, it is unclear how GLP‐1RAs exert their cardiorenal protective effects in patients with T2DM and whether an impact on inflammation and oxidative stress may contribute.…”

Section: Introductionmentioning

confidence: 99%

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Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Bray

Foster‐Davies

Salem

et al. 2021

Diabetes Obesity Metabolism

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Aim: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes.Methods: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG). Results: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m 2 and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference À0.54 mg/L [À0.75, À0.34]; standard mean difference [SMD] À0.39 [À0.62, À0.15]; SMD À0.84 [À1.61, À0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. Conclusions: There is strong evidence supporting clinically relevant antiinflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs. * Jonathan J. H. Bray and Harri Foster-Davies are co-first authors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Bray

Foster‐Davies

Salem

et al. 2021

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

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“…′ -deoxyguanosine, which are considered to be biomarkers of oxidative stress (75). That result provides evidence to the antioxidative-stress effect of SGLT2 inhibitors in patients with T2DM.…”

Section: Oxidative Stressmentioning

confidence: 54%

“…Subsequent clinical trials confirmed the anti-inflammatory effects of SGLT2 inhibitors (74). Recently, a meta-analysis involving 23 heterogeneously designed clinical trials showed that therapy using SGLT2 inhibitors could reduce the level of CRP, IL-6, TNFα significantly, and increase the adiponectin level significantly (75). Those results suggested that SGLT2 inhibitors can suppress inflammation, but the exact mechanisms remain unclear.…”

Section: Inflammatory and Metabolic Mechanisms Of Sglt2 Inhibitorsmentioning

confidence: 94%

Mechanisms and Perspectives of Sodium-Glucose Co-transporter 2 Inhibitors in Heart Failure

Zeng

Zhou

Liu

et al. 2021

Front. Cardiovasc. Med.

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Heart failure (HF) is a common complication or late-stage manifestation of various heart diseases. Numerous risk factors and underlying causes may contribute to the occurrence and progression of HF. The pathophysiological mechanisms of HF are very complicated. Despite accumulating advances in treatment for HF during recent decades, it remains an intractable clinical syndrome with poor outcomes, significantly reducing the quality of life and expectancy of patients, and imposing a heavy economic burden on society and families. Although initially classified as antidiabetic agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated reduced the prevalence of hospitalization for HF, cardiovascular death, and all-cause death in several large-scale randomized controlled clinical trials. These beneficial effects of SGLT-2 inhibitors can be attributed to multiple hemodynamic, inflammatory and metabolic mechanisms, not only reducing the serum glucose level. SGLT2 inhibitors have been used increasingly in treatment for patients with HF with reduced ejection fraction due to their surprising performance in improving the prognosis. In addition, their roles and mechanisms in patients with HF with preserved ejection fraction or acute HF have also attracted attention. In this review article, we discuss the possible mechanisms and applications of SGLT2 inhibitors in HF.

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“…Therefore, caution is dictated in interpretation of this biomarker. Additionally, studies investigating the effect of SGLT2i on oxidative stress, documented decrease of urine and serum levels of 8-iso-prostaglandin F2a (8-iso-PGF2a) and 8-Hydroxy-20-deoxyguanosine (8-OHdG) as well, two commonly used biomarkers of oxidative stress burden [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of a 12-Month Treatment with Glucagon-like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Oxidant and Antioxidant Biomarkers in Patients with Type 2 Diabetes

et al. 2021

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Imbalance between oxidative stress burden and antioxidant capacity is implicated in the course of atherosclerosis among type 2 diabetic patients. We addressed the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on levels of oxidant and antioxidant biomarkers. We recruited a total of 160 type 2 diabetics, who received insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40), or their combination (GLP-1RA+SGLT-2i) (n = 40). We measured at baseline, at 4 and at 12 months of treatment: (a) Thiobarbituric Acid Reactive Substances(TBARS), (b) Malondialdehyde (MDA), (c) Reducing Power (RP), (d) 2,2¢-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS) and (e) Total Antioxidant Capacity TAC). Dual treatment resulted in significant improvement of TBARS, MDA, and ABTS at four months compared with the other groups (p < 0.05 for all comparisons). At twelve months, all participants improved TBARS, MDA, and ABTS (p < 0.05). At 12 months, GLP1-RA and GLP-1RA+SGLT2-i provided a greater reduction of TBARS (−8.76% and −9.83%) compared with insulin or SGLT2i (−0.5% and 3.22%), (p < 0.05). GLP1-RA and GLP-1RA+SGLT-2i showed a greater reduction of MDA (−30.15% and −31.44%) compared with insulin or SGLT2i (4.72% and −3.74%), (p < 0.05). SGLT2i and GLP-1RA+SGLT2-i showed increase of ABTS (12.87% and 14.13%) compared with insulin or GLP1-RA (2.44% and −3.44%), (p < 0.05). Only combined treatment resulted in increase of TAC compared with the other groups after 12 months of treatment (p < 0.05).12-month treatment with GLP1-RA and SGLT2i resulted in reduction of biomarkers responsible for oxidative modifications and increase of antioxidant biomarker, respectively. The combination treatment was superior and additive to each separate agent and also the beneficial effects appeared earlier.

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A systematic review examining the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on biomarkers of inflammation and oxidative stress

Cited by 37 publications

References 64 publications

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Mechanisms and Perspectives of Sodium-Glucose Co-transporter 2 Inhibitors in Heart Failure

Effects of a 12-Month Treatment with Glucagon-like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Oxidant and Antioxidant Biomarkers in Patients with Type 2 Diabetes

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