scholarly journals How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Koichi Node
Keyword(s):  
Sglt2 Inhibitor ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Inhibitor Therapy ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials ◽  
Amino Terminal ◽  
Sodium Glucose Cotransporter ◽  
Diabetes Status ◽  
Cardiovascular Benefit

AbstractSodium–glucose cotransporter 2 (SGLT2) inhibitors are increasingly prescribed for the treatment of patients with type 2 diabetes to reduce the risk of cardiovascular events, including heart failure (HF). The mechanisms by which SGLT2 inhibitors reduce such risk are likely to be independent of diabetes status and improvement of glycemic control. In this commentary, based on recent mediation analyses of cardiovascular outcome trials with SGLT2 inhibitors, we discuss the prognostic role of a well-known HF-related biomarker, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients receiving SGLT2 inhibitors. Interestingly, the NT-proBNP concentration had a relatively small impact on the SGLT2 inhibitor-associated benefit on HF events, suggesting a limited value in measuring NT-proBNP concentrations to monitor effects on cardiovascular outcomes after initiation of SGLT2 inhibitor therapy. Instead, clinical factors, such as body weight and volume status, were prognostic for cardiovascular outcomes. As shown in some biomarker studies, short-term SGLT2 inhibitor treatment significantly improved volume and HF-related health status, despite the absence of a significant change in NT-proBNP concentration. Given the early and continuous risk reduction in HF events seen in the cardiovascular outcome trials with SGLT2 inhibitors, changes in these fundamental clinical parameters after initiation of SGLT2 inhibitor therapy, independent of NT-proBNP, could be more prognostic and could represent key determinants to identify responders or non-responders to SGLT2 inhibitors for cardiovascular outcomes. Thus, this commentary highlights the clinical importance of establishing how clinicians should monitor patients initiating SGLT2 inhibitor therapy to predict the expected cardiovascular benefit. Further detailed investigations and discussion to better understand this ‘‘black box’’ are urgently warranted.

scholarly journals Sodium-glucose cotransporter 2 inhibitors: extending the indication to non-diabetic kidney disease?

2020 ◽  
Vol 35 (Supplement_1) ◽  
pp. i33-i42 ◽  
Author(s):  
Claire C J Dekkers ◽  
Ron T Gansevoort
Keyword(s):  
Kidney Function ◽  
Kidney Diseases ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Cardiovascular Outcome ◽  
Medical Community ◽  
Haemoglobin A1c ◽  
Cardiovascular Outcome Trials ◽  
Beneficial Effects ◽  
Sodium Glucose Cotransporter

Abstract This year the medical community was pleasantly surprised by the results of the first large outcome trial that primarily examined the renal effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (CANA) in subjects with diabetes and impaired kidney function. The Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial showed that CANA, relative to placebo, reduces the risk for end-stage renal disease, doubling of creatinine or renal death by 34% [hazard ratio 0.66 (95% confidence interval 0.53–0.81]. These effects were consistent across baseline estimated glomerular filtration rate (eGFR) and haemoglobin A1c subgroups. In this review we combine the results of the CREDENCE trial with those of several cardiovascular outcome trials with SGLT2 inhibitors and show that, unexpectedly, patients with lower eGFR levels may have greater benefit with respect to cardiovascular outcome than patients with normal kidney function. The cardio- and renoprotective effects of SGLT2 inhibitors seem to be independent of their glucose-lowering effects, as shown in several post hoc analyses. In this review we discuss the alleged mechanisms of action that explain the beneficial effects of this novel class of drugs. Moreover, we discuss whether these findings indicate that this class of drugs may also be beneficial in non-diabetic chronic kidney diseases.

The Role of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure, Regardless of Diabetes Status: Focus on Cardiovascular Disease

2021 ◽  
pp. 106002802098511
Author(s):  
Filipe Ferrari ◽  
Vítor M. Martins ◽  
Rafael S. Scheffel ◽  
Anderson D. da Silveira ◽  
Marcelo Trotte Motta ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Data Extraction ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Diabetes Status ◽  
Neprilysin Inhibitor ◽  
Patients With Heart Failure

Objective: To provide clinical guidance and an overview of the available data on the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence of type 2 diabetes mellitus (T2DM). Data Sources: We searched the MEDLINE database via PubMed (from January 2015 to November 2020) for the following key terms: SGLT2 inhibitors, sodium-glucose co-transporter-2 inhibitors, SGLT2i, heart failure, and heart failure with reduced ejection fraction. Study Selection and Data Extraction: To be included in the review, the articles needed to assess the effects of SGLT2 inhibitors in the heart failure (HF) scenario. Data Synthesis: There is consistent evidence that SGLT2 inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization in patients with HFrEF, even in the absence of T2DM. On May 5, 2020, the U.S. Food and Drug Administration approved dapagliflozin for adults with HFrEF, regardless of the presence of T2DM, even in those patients on standard therapy, including an angiotensin receptor/neprilysin inhibitor. Relevance to Patient Care and Clinical Practice: The SGLT2 inhibitors are well tolerated, and their once-daily dosing without the need for adjustments is convenient. These drugs can be considered a major breakthrough in pharmacotherapy for HF, providing physicians with a new treatment approach to reduce major clinical outcomes. Conclusions: SGLT2 inhibitor therapy reduces CV death and hospitalizations in HFrEF patients regardless of T2DM. The decision to prescribe this class of drugs should not be determined by glycemic status.

scholarly journals The Efficacy of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors for the treatment of chronic diabetic macular oedema in vitrectomised eyes: a retrospective study

2018 ◽  
Vol 3 (1) ◽  
pp. e000130 ◽  
Author(s):  
Hiroki Mieno ◽  
Kazuhito Yoneda ◽  
Masahiro Yamazaki ◽  
Ryosuke Sakai ◽  
Chie Sotozono ◽  
...  
Keyword(s):  
Macular Oedema ◽  
Sglt2 Inhibitor ◽  
Diabetic Macular Oedema ◽  
Sglt2 Inhibitors ◽  
Rank Test ◽  
Sodium Glucose Cotransporter ◽  
Signed Rank ◽  
Before And After ◽  
Patients With Diabetes ◽  
Signed Rank Test

ObjectiveTo investigate the change of chronic diabetic macular oedema (DMO) in vitrectomised eyes when the administration of sodium–glucose cotransporter 2 (SGLT2) inhibitors is initiated as a systemic medical treatment.Methods and analysisThis study involved 10 eyes of five patients with chronic DMO lasting more than 6 months who had previously undergone vitrectomy and whose systemic medical treatments were newly changed to SGLT2 inhibitors. In this study, chronic DMO was defined as persistent diffuse macular oedema despite ophthalmic treatment in patients with diabetes. Patients who received antivascular endothelial growth factor therapy or steroids administration, or change of eye-drop medication from at 3 months before and after the initiation of SGLT2 inhibitors, were excluded. In this study, visual acuity (VA) and central retinal thickness (CRT, μm) prior to and at 3, 6 and 12 months after the initiation of SGLT2 inhibitors were retrospectively compared. The Wilcoxon signed-rank test was used for statistical analysis.ResultsIn the 10 treated eyes, from at baseline to at 3, 6 and 12 months after the initiation of SGLT2 inhibitor, median VA (logMAR) improved from 0.35 to 0.15 (p=0.038), 0.2 (p=0.157) and 0.2 (p=0.096), respectively, and median CRT significantly reduced from 500.5 µm to 410 µm (p<0.01), 378 µm (p<0.01) and 339 µm (p<0.01), respectively.ConclusionAlthough this study involved only five patients, our findings indicate that SGLT2 inhibitors might have structural efficacy for chronic DMO in vitrectomised eyes.

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