Efficacy and cardiovascular safety of SGLT2 Inhibitors

2020 ◽  
Vol 15 ◽  
Author(s):  
Cornelius James Fernandez ◽  
Abisha Graciano Nevins ◽  
Shasta Nawaz ◽  
Tahir Nazir ◽  
Fahmy W F Hanna
Keyword(s):  
Decision Process ◽  
Cardiovascular Events ◽  
Unmet Need ◽  
Clinical Decision ◽  
Sglt2 Inhibitors ◽  
Renal Protection ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

: Patients with diabetes continued to exhibit a high risk for cardiovascular and renal events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF). The latter has recently been recognised as a major cause of morbidity and mortality in patients with diabetes mellitus. There had been an unmet need for drugs with cardiovascular (including HF) and renal protection, with an expectation that an ideal diabetic drug should improve these end points. Moreover, an ideal drug should have weight lowering benefits. Recently published outcome trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) can reduce cardiovascular and renal events, together with statistically significant weight reduction. As a result, many recently published international guidelines have recommended SGLT2 inhibitors and GLP-1RAs in patients with diabetes and pre-existing cardiovascular disease (CVD). In this review we will critically analyse the efficacy and cardiovascular (CV) safety of SGLT2 inhibitors, based on the available literature to help position them in the clinical decision process.

scholarly journals Diabetes Drugs and Cardiovascular Event Reduction: A Paradigm Shift

2018 ◽  
Vol 12 (1) ◽  
pp. 46-50
Author(s):  
Erik M Kelly ◽  
Donald E Cutlip
Keyword(s):  
Clinical Practice ◽  
Cost Effectiveness ◽  
Paradigm Shift ◽  
Cardiovascular Events ◽  
Outcome Data ◽  
Review Article ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Effectiveness Data

This review article summarizes the recent cardiovascular outcome data for sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 analogues, which have been found to reduce cardiovascular events. We also detail the implications these new medications will have on clinical practice through a review of recent diabetes guidelines and cost-effectiveness data.

scholarly journals How Do SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitors and GLP-1 (Glucagon-Like Peptide-1) Receptor Agonists Reduce Cardiovascular Outcomes?

2020 ◽  
Vol 40 (3) ◽  
pp. 506-522 ◽  
Author(s):  
Matthew M.Y. Lee ◽  
Mark C. Petrie ◽  
John J.V. McMurray ◽  
Naveed Sattar
Keyword(s):  
Diabetes Mellitus ◽  
Mechanisms Of Action ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Left Ventricular Ejection ◽  
Cardiac Effects ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective: There is substantial interest in how GLP-1RA (glucagon-like peptide-1 receptor agonists) and SGLT2 (sodium-glucose cotransporter 2) inhibitors reduce cardiovascular and renal events; yet, robust mechanistic data in humans remain sparse. We conducted a narrative review of published and ongoing mechanistic clinical trials investigating the actions of SGLT2 inhibitors and GLP-1RAs to help the community appreciate the extent of ongoing work and the variety and design of such trials. Approach and Results: To date, trials investigating the mechanisms of action of SGLT2 inhibitors have focused on pathways linked to glucose metabolism and toxicity, hemodynamic/volume, vascular and renal actions, and cardiac effects, including those on myocardial energetics. The participants studied have included those with established cardiovascular disease (including coronary artery disease and heart failure), liver disease, renal impairment, obesity, and hypertension; some of these trials have enrolled patients both with and without type 2 diabetes mellitus. GLP-1RA mechanistic trials have focused on glucose-lowering, insulin-sparing, weight reduction, and blood pressure–lowering effects, as well as possible direct vascular, cardiac, and renal effects of these agents. Very few mechanisms of action of SGLT2 inhibitors or GLP-1RAs have so far been convincingly demonstrated. One small trial (n=97) of SGLT2 inhibitors has investigated the cardiac effects of these drugs, where a small reduction in left ventricular mass was found. Data on vascular effects are limited to one trial in type 1 diabetes mellitus, which suggests some beneficial actions. SGLT2 inhibitors have been shown to reduce liver fat. We highlight the near absence of mechanistic data to explain the beneficial effects of SGLT2 inhibitors in patients without diabetes mellitus. GLP-1RAs have not been found to have major cardiovascular mechanisms of action in the limited, completed trials. Conflicting data around the impact on infarct size have been reported. No effect on left ventricular ejection fraction has been demonstrated. Conclusions: We have tabulated the extensive ongoing mechanistic trials that will report over the coming years. We report 2 exemplar ongoing mechanistic trials in detail to give examples of the designs and techniques employed. The results of these many ongoing trials should help us understand how SGLT2 inhibitors and GLP-1RAs improve cardiovascular and renal outcomes and may also identify unexpected mechanisms suggesting novel therapeutic applications.

scholarly journals Glycemic Variability Impacted by SGLT2 Inhibitors and GLP 1 Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (18) ◽  
pp. 4078
Author(s):  
Heeyoung Lee ◽  
Se-eun Park ◽  
Eun-Young Kim
Keyword(s):  
Meta Analysis ◽  
Glycemic Variability ◽  
Mean Amplitude ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
The Mean ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Mean Blood Glucose

To investigate the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists on glycemic variability (GV), the mean amplitude of glucose excursion (MAGE), mean blood glucose (MBG) levels, and percentage of time maintaining euglycemia were evaluated. Randomized controlled trials evaluating the efficacy of SGLT-2 inhibitors and GLP-1 agonists for treating people with diabetes were selected through searches of PubMed, EMBASE, and other databases. Sixteen studies were finally analyzed. There were no differences in the reductions in MAGE after treatment with SGLT-2 inhibitors or GLP-1 agonists (standardized mean difference (SMD) = −0.59, 95% CI = −0.82 to −0.36 vs. SMD = −0.43, 95% CI = −0.51 to −0.35, respectively), and treatment with SGLT-2 inhibitors was associated with an increased reduction in MBG levels (SMD = −0.56, 95% CI = −0.65 to −0.48, p < 0.00001). Monotherapy and add-on therapy with medications were correlated with MAGE and MBG level reductions. In conclusion, SGLT-2 inhibitors and GLP-1 agonists were associated with a reduction in GV and could be alternatives for treating people with diabetes.

scholarly journals Anti-diabetic Agents and the Potentials for Reducing Cardiovascular Risks in Type-2 Diabetes Mellitus

2021 ◽  
Vol 7 (3) ◽  
pp. 208-226
Author(s):  
IU Ezeani ◽  
A Eregie ◽  
AE Ohwovoriole
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Mechanisms Of Action ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Recent reports from Cardiovascular Outcome Trials (CVOTs) revealed that some newer anti-diabetic drugs impact Major Adverse Cardiovascular Events (MACE). These medications include the Sodium-Glucose Co-Transporter (SGLT2) inhibitors and the Glucagon-like Peptide-1 (GLP-1) receptor agonists. There is a need for a review of the mechanisms of action of these drugs, in addition to their glucose-lowering effects and CV benefits. This review paper aims to explore the cardio-protective effects and CV risks of anti-diabetic medications, their mechanisms of action and the CV benefits evidenced by CVOTs. Using internet search, with search items such as Type 2 Diabetes mellitus, cardiovascular risk factors, cardiovascular outcome trials, major adverse cardiovascular events, sodium-glucose transporter-2 inhibitors, glucagon-like peptide-1 receptor agonist, the Google Scholar, EMBASE, PubMed, Medline, Web MD, and Scopus were checked for various relevant published articles. Analyses of the results of multiple CVOTs from various parts of the world were considered. These CVOTs were reviewed to assess the role of anti-diabetic agents in reducing cardiovascular risk in patients with T2DM. The SGLT2 inhibitors and GLP1 agonists were found to be beneficial in lowering MACE when compared with placebo. This is in addition to their anti-hyperglycaemic benefits. In conclusion, SGLT2 inhibitors and GLP-1 agonists confer dramatic beneficial CV risk reduction on patients with T2DM, as shown by the various CVOTs. This is in addition to their anti-hyperglycaemic effects. This remarkable benefit justifies the need by various guidelines to adopt them as second line agents to metformin in managing patients with T2DM.

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