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Subtype-Dependent Reporting of Stroke With SGLT2 Inhibitors: Implications From a Japanese Pharmacovigilance Study.
Abstract Volume depletion as an adverse events (AE) caused by sodium-glucose cotransporter-2 inhibitors (SGLT2i) because of their diuretic effect may raise the concern about the risk of lacunar stroke; however, an earlier meta-analysis reported no significant increase in the incidence of stroke without clearly distinguishing stroke subtypes. Here, aiming to investigate subtype-wise reporting of stroke potentially related to SGLT2i treatment, we conducted a disproportionality analysis using the Japanese Adverse Drug Event Report database, which contains approximately 500 000 cases recorded between April 2004 and M...
Source: The Journal of Clinical Pharmacology - December 1, 2019 Category: Drugs & Pharmacology Authors: Sato K, Mano T, Iwata A, Toda T Tags: J Clin Pharmacol Source Type: research

Potential Therapeutic Effects of Sodium Glucose-linked Cotransporter 2 Inhibitors in Stroke.
CONCLUSIONS: It is unlikely that SGLT inhibitors have a positive or negative effect on stroke risk, but the question that remains unanswered is whether SGLT inhibitors can yield a protective effect after acute ischemic stroke. Future observational studies and registries may be the first step to help answer this question. (Clin Ther. 2020; XX:XXX-XXX) © 2020 Elsevier HS Journals, Inc. PMID: 33008610 [PubMed - as supplied by publisher]
Source: Clinical Therapeutics - September 28, 2020 Category: Drugs & Pharmacology Authors: Al Hamed FA, Elewa H Tags: Clin Ther Source Type: research

Comment on "Subtype-Dependent Reporting of Stroke With SGLT2 Inhibitors: Implications From a Japanese Pharmacovigilance Study".
PMID: 32408385 [PubMed - as supplied by publisher]
Source: The Journal of Clinical Pharmacology - May 13, 2020 Category: Drugs & Pharmacology Authors: Cure E, Cumhur Cure M Tags: J Clin Pharmacol Source Type: research

EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.
Abstract During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease. In the majority of CV outcome studies, CV ris...
Source: Clinical Therapeutics - May 18, 2016 Category: Drugs & Pharmacology Authors: Schernthaner G, Schernthaner-Reiter MH, Schernthaner GH Tags: Clin Ther Source Type: research

Exploring heterogeneities of cardiovascular efficacy and effectiveness of SGLT2 inhibitors in patients with type 2 diabetes: an umbrella review of evidence from randomized clinical trials versus real-world observational studies
ConclusionOS presented significant benefits of SGLT2 inhibitors both on primary and secondary preventions of MACE, MI, stroke, ACM, CVM, and HHF; RCTs did not. Given the spectrum of T2D patient characteristics and the strength of overall evidence, our review underscored the importance of constant integration of all available information and critical interpretation of all inconsistencies to optimize evidence-based diabetes care.
Source: European Journal of Clinical Pharmacology - June 7, 2022 Category: Drugs & Pharmacology Source Type: research

The effect of SGLT2 inhibitors on cardiovascular events and renal function.
Abstract Introduction Sodium-glucose co-transporters-2inhibitors have emerged as a very promising antidiabetic drug class, with data from the two available cardiovascular trials of this class suggesting remarkable benefits in terms of cardiovascular events, total mortality and renal outcomes. Areas covered Data point toward clinically meaningful benefits from SGLT-2inhibition on a variety of cardiovascular risk factors. Empagliflozin, and to a lesser extent canagliflozin, resulted in significant reductions of an abundance of cardiovascular mortality and morbidity endpoints. SGLT-2inhibitors were also found to redu...
Source: Pharmacological Reviews - August 22, 2017 Category: Drugs & Pharmacology Authors: Imprialos KP, Stavropoulos K, Doumas M, Karagiannis A, Athyros VG Tags: Expert Rev Clin Pharmacol Source Type: research

Canagliflozin Inhibits Human Endothelial Cell Proliferation and Tube Formation
In conclusion, the present study identified canagliflozin as a potent inhibitor of human EC proliferation. The anti-proliferative action of canagliflozin is observed in ECs isolated from both the venous and arterial circulation, and is partly due to the blockade of cyclin A expression. In addition, this study found that canagliflozin inhibits tube formation in cultured ECs and mouse aortic rings. Notably, these actions are specific for canagliflozin and not seen with other SGLT2 inhibitors. The ability of canagliflozin to exert these pleiotropic effects on EC function may contribute to both the adverse and salutary actions...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Insights Into the Results of Sotagliflozin Cardiovascular Outcome Trials: Is Dual Inhibition the Cherry on the Cake of Cardiorenal Protection?
AbstractSotagliflozin is a dual sodium-glucose co-transporter (SGLT) 2 inhibitor, manifesting a 20-fold higher inhibitory activity for SGLT2 than for SGLT1. Differences in SGLT2 over SGLT1 selectivity of the available agents have been proposed to relate to variability in efficacy and safety characteristics. In contrast to other SGLT2  inhibitors, the cardiorenal effects of sotagliflozin in type 2 diabetes had not been explored until recently, when the results of SOLOIST-WHF (focusing on heart failure [HF] outcomes) and SCORED (focusing on renal outcomes) were published. In SOLOIST-WHF, sotagliflozin reduced the risk of th...
Source: Drugs - July 7, 2021 Category: Drugs & Pharmacology Source Type: research

Empagliflozin: a new treatment option for patients with type 2 diabetes mellitus.
Authors: Dailey GE Abstract Empagliflozin is an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by decreasing renal glucose reabsorption and promoting urinary glucose excretion. In clinical trials, empagliflozin demonstrated significant improvements in glycemic control, as monotherapy and in combination regimens. In addition, empagliflozin was associated with weight loss and moderate reductions in blood pressure. In the EMPA-REG OUTCOME study, empagliflozin significantly reduced the risk of the composite primary endpoint of cardiovascular death, no...
Source: Drugs of Today - October 23, 2015 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Cardiovascular outcomes with canagliflozin - is it on the CANVAS?
Authors: Doggrell S Abstract INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (the 'gliflozins') promote the excretion of glucose from the kidney to lower HbA1c. Empagliflozin was the first gliflozin shown to improve cardiovascular and renal outcomes in subjects with type 2 diabetes and cardiovascular disease. Areas covered: In the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, there were improvements in the primary cardiovascular and exploratory renal outcomes with canagliflozin, compared to placebo. The safety outcome finding, which was of most interest, was that there was a higher...
Source: Expert Opinion on Pharmacotherapy - December 20, 2017 Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

Dapagliflozin and cardiovascular outcomes: anything else to DECLARE?
Authors: Raschi E, Poluzzi E, Marchesini G, De Ponti F Abstract INTRODUCTION: Individuals with type 2 diabetes mellitus (T2DM) have increased cardiovascular risk with regulatory agencies requiring cardiovascular outcome trials (CVOTs) for the approval of new antidiabetic drugs. Areas covered: In this paper, the authors critically discuss the background, trial design, results and implications of a recent CVOT [NCT01730534; DECLARE-TIMI 58 study], which demonstrated that dapagliflozin was non-inferior to placebo in terms of major adverse cardiovascular events, and superior for the occurrence of hospitalization for he...
Source: Expert Opinion on Pharmacotherapy - March 30, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials
ConclusionsThere were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.
Source: European Journal of Clinical Pharmacology - May 3, 2021 Category: Drugs & Pharmacology Source Type: research

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