scholarly journals Cardiovascular Outcomes in Trials of New Antidiabetic Drug Classes

2021 ◽  
Vol 7 ◽  
Author(s):  
Chris Wai Hang Lo ◽  
Yue Fei ◽  
Bernard Man Yung Cheung
Keyword(s):  
Heart Failure ◽  
Cardiovascular Complications ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Second Line ◽  
Antidiabetic Drug ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Receptor Agonists ◽  
Drug Classes

Type 2 diabetes is among the most prevalent chronic diseases worldwide and the prevention of associated cardiovascular complications is an important treatment goal. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are second-line options after metformin, while cardiovascular outcome trials have been conducted to establish the cardiovascular safety of these antidiabetic drug classes. SGLT2 inhibitors have been shown to have the best overall mortality, renal and cardiovascular outcomes. Reduction in hospitalisation for heart failure is particularly consistent. GLP-1 receptor agonists have also showed some benefits, especially in stroke prevention. DPP-4 inhibitors showed neutral effects on cardiovascular outcomes, but may increase the incidence of heart failure. Favourable outcomes observed in trials of SGLT2 inhibitors mean that these should be the preferred second-line option. DPP-4 inhibitors are useful for patients with diabetes at low cardiovascular risk.

scholarly journals The Impact of Antidiabetic Therapies on Diastolic Dysfunction and Diabetic Cardiomyopathy

2020 ◽  
Vol 11 ◽  
Author(s):  
Keshav Gopal ◽  
Jadin J. Chahade ◽  
Ryekjang Kim ◽  
John R. Ussher
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Dipeptidyl Peptidase 4 ◽  
Reduced Ejection Fraction ◽  
The Impact

Diabetic cardiomyopathy is more prevalent in people with type 2 diabetes mellitus (T2DM) than previously recognized, while often being characterized by diastolic dysfunction in the absence of systolic dysfunction. This likely contributes to why heart failure with preserved ejection fraction is enriched in people with T2DM vs. heart failure with reduced ejection fraction. Due to revised mandates from major health regulatory agencies, all therapies being developed for the treatment of T2DM must now undergo rigorous assessment of their cardiovascular risk profiles prior to approval. As such, we now have data from tens of thousands of subjects with T2DM demonstrating the impact of major therapies including the sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors on cardiovascular outcomes. Evidence to date suggests that both SGLT2 inhibitors and GLP-1R agonists improve cardiovascular outcomes, whereas DPP-4 inhibitors appear to be cardiovascular neutral, though evidence is lacking to determine the overall utility of these therapies on diastolic dysfunction or diabetic cardiomyopathy in subjects with T2DM. We herein will review the overall impact SLGT2 inhibitors, GLP-1R agonists, and DPP-4 inhibitors have on major parameters of diastolic function, while also highlighting the potential mechanisms of action responsible. A more complete understanding of how these therapies influence diastolic dysfunction will undoubtedly play a major role in how we manage cardiovascular disease in subjects with T2DM.

SGLT2 inhibitors: A revolution in therapeutics of a major Non-Communicable Disease

2021 ◽  
pp. 1-3
Author(s):  
Muhammad Sami Khan
Keyword(s):  
Heart Failure ◽  
Health Care ◽  
Health Care Providers ◽  
Communicable Disease ◽  
Health Care Expenditure ◽  
Health Care Expenditures ◽  
Sglt2 Inhibitors ◽  
Care Providers ◽  
Cardiovascular Outcome Trials ◽  
Non Communicable Disease

Pakistan is facing an exorbitant burden of Non-communicable diseases among which Cardiovascular diseases are the most prominent which has not only caused mortality but also posed a big threat on weakened economy and health care system of the country. Amidst of this growing crisis, Sodium glucose co-transporter 2 (SGLT2) inhibitors emerge as a ray of hope by reducing simultaneously the complication and health care expenditure associated with the management of this major mortality-bringing Non-communicable disease. SGLT2 inhibitors, including Dapagliflozin and Empagliflozin, are evidence-based standardized novel anti-diabetic agents tested in cardiovascular outcome trials namely DAPA-HF and EMPEROR-Reduced, when added to standard care in heart failure patients with reduced ejection fraction, provides breakthrough heart failure outcomes and also addresses massive health care expenditures. This novel finding provides an impetus to promote its beneficial effects among health care providers and early implementation. Continuous....

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 Series: Cardiovascular outcome trials for diabetes drugs Saxagliptin and SAVOR-TIMI 53

2019 ◽  
Vol 19 (1) ◽  
pp. 34-36
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Cardiovascular Outcome ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Increased Risk ◽  
Cardiovascular Outcome Trial

SAVOR-TIMI 53 was the first FDA-mandated cardiovascular outcome trial to be presented and published. It compared saxagliptin and placebo in 16,492 patients with type 2 diabetes. SAVOR-TIMI 53 demonstrated non-inferiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) but not superiority. An unexpected statistically significant increase in adjudicated hospitalisation for heart failure was seen in the saxagliptin group. Post hoc analysis demonstrated that subjects at greatest risk for hospitalisation for heart failure had previous heart failure, an estimated glomerular filtration rate <60 mL/min, or elevated baseline levels of N-terminal pro-B type natriuretic peptide. As other dipeptidyl peptidase 4 (DPP-4) inhibitors are available which have not been associated with an increased risk of hospitalisation for heart failure, saxagliptin should be avoided in patients with heart failure or a reduced estimated glomerular filtration rate.

scholarly journals Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261986
Author(s):  
Ning Li ◽  
Guowei Zhou ◽  
Yawei Zheng ◽  
Dan Lv ◽  
Xiangjun Zhu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Ejection Fraction ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Atherosclerotic Cardiovascular Disease ◽  
Reduced Ejection Fraction ◽  
Stage 4

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

scholarly journals The Effects of DPP-4 Inhibitors, GLP-1RAs, and SGLT-2/1 Inhibitors on Heart Failure Outcomes in Diabetic Patients With and Without Heart Failure History: Insights From CVOTs and Drug Mechanism

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaohui Pan ◽  
Shishi Xu ◽  
Juan Li ◽  
Nanwei Tong
Keyword(s):  
Heart Failure ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Drug Mechanism ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes ◽  
History Of ◽  
Glucagon Like Peptide 1 ◽  
Diabetes Drug

Patients with type 2 diabetes (T2D) have a higher risk of heart failure (HF) than healthy people, and the prognosis of patients with diabetes and current or previous HF is worse than that of patients with only diabetes. We reviewed the HF outcomes in recently published cardiovascular outcome trials (CVOTs) of three new classes of anti-diabetic agents, namely, dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like-peptide 1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 inhibitors (SGLT-2is) or SGLT-2 and SGLT-1 dual inhibitors and divided the patients into two groups based on the history of HF (with or without) and analyzed their risks of HHF based on the receipt of the aforementioned anti-diabetes drug types. Since the follow-up period differed among the trials, we expressed the rate of HHF as events/1,000 person-years to describe the HF outcome. At last we pooled the data and analyzed their different effects and mechanisms on heart failure outcomes. Although DPP-4is did not increase the risk of HHF in T2D patients with a history of HF, they were associated with a significantly higher risk of HHF among patients without history of HF. Some GLP-1RAs reduced the risk of macrovascular events, but none of these drugs reduced the risk of HHF in patients with T2D irrespective of their HF history. It was not clarified whether SGLT-1/2is can improve the prognosis of macrovascular events in patients with T2D, but these drugs reduced the risk of HHF regardless of patients’ histories of HF. This information may be useful or referential for the “precise” selection of hyperglycemic medications. Further researches still needed to clarify the mechanisms of these anti-diabetic medications.

scholarly journals Impact of canagliflozin in natriuretic peptides in patients with type 2 diabetes after hospitalization for acute heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Martin Dorado ◽  
R Gonzalez Manzanares ◽  
J.C Castillo Dominguez ◽  
J Lopez Aguilera ◽  
J Perea ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Acute Decompensated Heart Failure ◽  
Signs And Symptoms ◽  
Sglt2 Inhibitors ◽  
Control Group ◽  
Dipeptidyl Peptidase 4 ◽  
Reduced Ejection Fraction

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated to reduce the risk of hospitalization for heart failure (HF) in patients with type 2 diabetes mellitus (T2D). We aimed to assess the changes in N-terminal pro-B-type natriuretic peptide (NT-ProBNP) concentrations in a cohort of patients hospitalized for HF according to whether or not they received canagliflozin at discharge. Methods This cohort study included all patients with T2D admitted for HF from January 2017 to December 2019 in a single center. We excluded patients whose treatment with SGLT2 inhibitors were contraindicated (eGFR ≤45 ml/min/1.73 m2) and those who had other SGLT2 inhibitors than canagliflozin in their treatment at discharged. All patients had received a primary diagnosis of acute decompensated heart failure, including signs and symptoms of fluid overload and a concentration of NT-ProBNP of 1400 pg/mL at least. NT-ProBNP concentrations were collected at 3 months, 6 months, and 1 year after hospitalization with laboratory records if available. The aim of this study is to compare mean NT-ProBNP levels at hospital discharge and 3, 6 and 12 moths of follow-up in patients treated with and without canagliflozin. Results We included a total of 102 patients, 45 patients (44.1%) were prescribed canagliflozin and the remaining 57 (55.9%) were not prescribed any SGLT2 inhibitors (control group). There were no significant differences in clinical and comorbidities in both groups, except for age; slightly younger in the canagliflozin group (69,2±10,3 vs 73,2±11,1; p=0,04). Treatment at discharge was also similar, patients in the control group received more dipeptidyl peptidase-4 (DPP-4) inhibitors (21.1% vs 6.7%; p=0.04). Low rate of patients received sacubitril-valsartan (15,6%) in the canagliflozin group and 14% in the control group. More than a half of patients in both groups have HF with reduced ejection fraction. Mean levels of peptides were similar in both groups at hospital admission and discharge. During the first period of 3 months, we observed a decreased of NT-ProBNP concentration in both groups, but significantly inferior in canagliflozin group (p&lt;0,001). At 6 and 12 months, NT-ProBNP levels were practically maintained in patients treated with canagliflozin, whereas levels in patients in the control group were increased. Difference in both groups at a 12 month-period was significantly superior (p=0,004), with a median reduction of concentration levels at discharge of 64.3% in the canagliflozin group and 15,8% in control group. There were no differences in patients with HF from those with reduced ejection fraction and preserved. Conclusions Canagliflozin therapy at discharge was associated with a significant reduction in NT-ProBNP concentration in patients with diabetes after hospitalization for HF. FUNDunding Acknowledgement Type of funding sources: None. NT-ProBNP according to canagliflozin

Cardio-protective Effects of Glucagon-like Peptide-1 Receptor Agonists: An Overview of Systematic Reviews and Publication Overlap

2021 ◽  
Vol 27 ◽  
Author(s):  
Stefanos Zafeiropoulos ◽  
Areti Pagiantza ◽  
Ioannis Doundoulakis ◽  
Nikolaos Stalikas ◽  
Ioannis Farmakis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Reviews ◽  
Cardiovascular Events ◽  
Methodological Quality ◽  
Cardiovascular Outcomes ◽  
Cochrane Library ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a new antihyperglycemic class with the demonstrated advantage of reducing major adverse cardiovascular events (MACE) among individuals with type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease or high cardiovascular risk. Objective: Τo summarize the evidence of systematic reviews (SRs) that assess MACE (cardiovascular mortality, nonfatal myocardial infarction and stroke) and hospitalizations for heart failure in GLP-1RAs-treated patients and to evaluate possible overlap in pertinent SRs. Methods: We performed a comprehensive search via MEDLINE, Cochrane Library, and PROSPERO databases up to February 23, 2020 for SRs examining cardiovascular outcomes of GLP-1RAs in T2DM patients. Three independent authors extracted data and assessed the methodological quality of the included SRs using the ROBIS tool. Results : We found 37 SRs – published between 2009 and 2020 in English – of which 35 collected data only from randomized clinical trials while two from observational studies as well. The methodological quality of the 37 SRs ranged from low to high while only 3 have evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. All the included SRs showed cardiovascular safety of GLP-1RAs while the latest ones demonstrated reduction in composite MACE endpoint as well as its every individual component and heart failure hospitalizations. Conclusion: In the first overview of SRs about cardiovascular outcomes of GLP-1RAs, they proved favorable effects on reducing cardiovascular events in T2DM patients. There are, however, many overlapping reviews based on relatively few cardiovascular outcomes trials.

Sign in / Sign up

Export Citation Format

Share Document