Clinical implications of current cardiovascular outcome trials with sodium glucose cotransporter-2 (SGLT2) inhibitors

2018 ◽  
Vol 272 ◽  
pp. 33-40 ◽  
Author(s):  
Soo Lim ◽  
Robert H. Eckel ◽  
Kwang Kon Koh
Keyword(s):  
Sglt2 Inhibitors ◽  
Cardiovascular Outcome ◽  
Clinical Implications ◽  
Cardiovascular Outcome Trials ◽  
Sodium Glucose Cotransporter

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.

scholarly journals Emerging glucose-lowering therapies: a guide for cardiologists

Heart ◽  
2019 ◽  
Vol 106 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Gaurav S Gulsin ◽  
Matthew P M Graham-Brown ◽  
Melanie J Davies ◽  
Gerry P McCann
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Practice ◽  
Large Scale ◽  
Cardiovascular Outcome ◽  
Glucose Lowering ◽  
Cardiovascular Outcome Trials ◽  
Sodium Glucose Cotransporter ◽  
Emerging Treatments ◽  
Glucagon Like Peptide 1 ◽  
Safety Considerations

In recent large-scale cardiovascular outcome trials, two new classes of glucose-lowering medications—sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs)—demonstrated cardiovascular benefits in adults with type 2 diabetes mellitus (T2DM). These findings have prompted growing optimism among clinicians regarding the potential for these agents to reduce the burden of cardiovascular disease in people with T2DM. GLP-1RAs and SGLT2i are now advocated as second-line agents in European and US guidelines for management of both hyperglycaemia and for primary prevention of cardiovascular disease in people with T2DM. Given the high prevalence of T2DM in patients with cardiovascular disease, cardiologists will increasingly encounter these agents in routine clinical practice. In this review, we summarise evidence from cardiovascular outcome trials of GLP-1RAs and SGLT2i, give practical advice on prescribing and detail safety considerations associated with their use. We also highlight areas where further work is needed, giving details on active clinical trials. The review aims to familiarise cardiologists with these emerging treatments, which will be increasingly encountered in clinical practice, given the expanding representation of T2DM in patients with cardiovascular disease. Whether these drugs will be initiated by cardiologists remains to be determined.

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