Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diabetes Drugs and Cardiovascular Safety.

ABSTRACT: Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

SUBMITTER: Bae JC

PROVIDER: S-EPMC4923407 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Diabetes Drugs and Cardiovascular Safety.

Bae Ji Cheol JC

Endocrinology and metabolism (Seoul, Korea) 20160610 2

Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiova ...[more]

PMID: 27302713

Similar Datasets

Cardiovascular outcomes and safety with antidiabetic drugs.

Project description:Type 2 diabetes is a debilitating disease that impacts the life expectancy, quality of life, and health of an individual. Cardiovascular disease (CVD) is a common diabetes-associated complication and a principal cause for death in diabetic patients. This review aims to investigate and summarize the effect of Type 2 diabetes mellitus (T2DM) medications on CVD issues. A comprehensive literature review mainly from level 1 evidence was performed. Thirty-seven articles were extracted from Google Scholar, ScienceDirect, ProQuest, and PubMed Database using a combination of keywords. The findings suggest that different glucose-lowering agents have been tested for their efficacy and safety in T2DM with CVD. Some of the recent trials such as the "United Kingdom Prospective Diabetes Study," "Empagliflozin (EMPA) Cardiovascular (CV) Outcome Event Trial in T2DM Patients-Removing Excess Glucose" (EMPA-REG OUTCOME), "Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results," and "Trial to Evaluate CV and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes" (SUSTAIN6) have shed important light on this vital clinical concern, thus demonstrating a convincing effect of liraglutide, semaglutide, and EMPA on CVD outcomes, while metformin is thought to be the first-line optimal oral agent to manage Type 2 diabetics. Some classes of drugs demonstrate CV protection, some of them may be a result of a class effect, and some differences might be based on the population enrolled individually. Most of the trials failed to show a significant benefit with regard to mortality and morbidity in spite of intensive glycemic control. This study, therefore, enabled us to develop a guide of potential antidiabetic medication that can influence or promote CV health. Health professionals in future should weigh the CV risk against possible advantages while prescribing antidiabetic medications.

| S-EPMC6124835 | biostudies-other

Cardiovascular effects of anti-diabetes drugs.

Project description:IntroductionCardiovascular disease remains the major contributor to morbidity and mortality in diabetes. From the need to reduce cardiovascular risk in diabetes and to ensure that such risk is not exacerbated by drug treatments, governmental regulators and drug manufacturers have focused on clinical trials evaluating cardiovascular outcomes.Areas coveredFindings from mechanistic and clinical trials of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors will be reviewed. These drug classes will be compared within the context of available cardiovascular outcomes data. Clinical implications of new study regulations will be examined.Expert opinionRecent cardiovascular studies provide a more comprehensive evaluation of specific anti-diabetes therapy in individuals with high cardiovascular risk. Long-term effects of anti-hyperglycemic agents in patients with lower cardiovascular risk are still speculative. Historical data supports continued use of metformin as a first-line agent. DPP-4 inhibitors and GLP-1 receptor agonists appear to have neutral effects on cardiovascular outcomes. The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin.

| S-EPMC5036275 | biostudies-literature

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

Project description:ObjectiveTo analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.DesignNetwork meta-analysis.Data sourcesBibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.Study selectionAll large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.Data extractionThe primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.Data synthesis31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.ConclusionsAlthough uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

| S-EPMC3019238 | biostudies-literature

Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019.

Project description:Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure, and mortality have been reported with the use of these drugs. It is important to have knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.

| S-EPMC7228893 | biostudies-literature

Dapagliflozin: Cardiovascular Safety and Benefits in Type 2 Diabetes Mellitus.

Project description:Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin, canagliflozin, and empagliflozin, are a promising new therapy in the treatment of type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia thus improving glycemic control and they offer some beneficial effects on the cardiovascular (CV) system which can benefit patients with heart failure in addition toT2DM. The United States Food and Drug Administration requires new diabetes mellitus therapies to show a CV safety profile. Empagliflozin was the first SGLT2i that, when added to the standard of care for patients withT2DM at high risk for CV events, showed improved CV outcomes including reduced deaths from CV causes. Evidence also exists in favor of dapagliflozin for use in patients with T2DM with CV risk factors and heart failure. This review focuses on the effects, safety, and benefits of dapagliflozin on the CV system. Clinical trials have shown that dapagliflozin improves glycemic control without variation. It is safe and well-tolerated in the general population including older patients and those with high-risk CV factors or preexisting CV disease. There may be a renal protective role by an unknown mechanism. Dapagliflozin also lowers blood pressure due to its natriuresis effect. It improves levels of visceral fat and reduces body weight, and thus ameliorates metabolic syndrome. Dapagliflozin reduces oxidative stress and may delay atherosclerosis. Recent findings indicate SGLT2is may also reduce the atrial natriuretic peptide levels. Additional trials are required to validate these benefits and further evaluate if these are class effects. Trials such as DECLARE-TIMI58 are ongoing to evaluate the CV outcomes of dapagliflozin. More research is needed to design better antihyperglycemic regimes with clinical benefits in addition to good glycemic control.

| S-EPMC5716679 | biostudies-literature

Type 2 diabetes mellitus development programs in the new regulatory environment with cardiovascular safety requirements.

Project description:For type 2 diabetes mellitus treatment and clinical development, proper evaluation of cardiovascular risk has been required by regulatory agencies (eg, the US Food and Drug Administration) since cardiovascular safety is very important in this patient population. The US Food and Drug Administration issued general guidelines for cardiovascular safety evaluation that outlined the requirements considered adequate for cardiovascular safety evaluation. However, there are multiple options to obtain the data and fulfill these requirements. In this paper, we outline the potential pathways and challenges in various aspects of cardiovascular safety evaluation in type 2 diabetes clinical development, including study design, populations, and endpoints. Specifically, we discuss some challenges in statistical analysis which have implications for the design, implementation, and interpretation of these outcome studies.

| S-EPMC4516202 | biostudies-other

Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet.

Project description:Purpose of reviewThe purpose is to review evidence on cardiovascular risks and benefits of new treatments for type 2 diabetes mellitus.Recent findingsIn response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Two studies of GLP-1 receptor agonists-one of liraglutide and one of semaglutide-have shown cardiovascular benefit relative to placebo, and one study of the SGLT-2 inhibitor empagliflozin has shown benefit. The other published cardiovascular outcome studies of the newest drug classes have generally supported safety, apart from an as-yet unresolved safety concern about increased rates of heart failure with DPP-4 inhibitors. Recent research suggests the thiazolidinedione pioglitazone may have beneficial effects on some cardiovascular outcomes as well, but these are counterbalanced by a known increase of the risk of heart failure with this drug. In general, more prospective randomized trial data is now available regarding the cardiovascular effects of the newer diabetes drugs than on the older drug classes. New evidence suggests that the newest diabetes drugs are safe from a cardiovascular perspective. Evidence on benefit from at least some members of the GLP-1 receptor agonist and SGLT-2 inhibitor classes is encouraging but not yet decisive.

| S-EPMC5509052 | biostudies-literature

Advances in the management of cardiovascular risk for patients with type 2 diabetes: perspectives from the Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes.

Project description:Diabetes is a global health emergency projected to affect 642 million people by 2040. Type 2 diabetes (T2D) represents 90% of diabetes cases and is associated with a range of cardiovascular (CV) risk factors that are more than double the incidence of CV disease and significantly increase mortality rates. Diabetes treatments have typically focused on improving glycemic control but their effect on CV outcomes has remained uncertain. In 2008, the US Food and Drug Administration (FDA) looked to address this knowledge gap and mandated CV outcome trials (CVOTs) for all new antidiabetic therapies. In 2015, EMPA-REG OUTCOME® became the first CVOT to present results for a sodium/glucose cotransporter 2 (SGLT2; also known as SLC5A2) inhibitor, empagliflozin. Subsequently, a regional meeting of the Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes (ACROSS T2D) brought together a respected faculty of international experts and 150 physicians from 14 countries to discuss the current unmet medical needs of patients with T2D, the results from the EMPA-REG OUTCOME study and the implications of these results for clinical practice. This article summarizes the current scientific evidence and the discussions that took place at the ACROSS T2D regional meeting, which was held in Vienna, Austria, on May 30, 2016.

| S-EPMC5245806 | biostudies-other

Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events.

Project description:BackgroundThe cardiovascular (CV) safety of linagliptin was evaluated in subjects with type 2 diabetes (T2DM).MethodsPre-specified patient-level pooled analysis of all available double-blind, randomized, controlled trials, ≥ 12 weeks' duration (19 trials, 9459 subjects) of linagliptin versus placebo/active treatment. Primary end point: composite of prospectively adjudicated CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina (4P-MACE). Hospitalization for congestive heart failure (CHF) was also evaluated; adjudication of CHF was introduced during the phase 3 program (8 trials; 3314 subjects). 4P-MACE was assessed in placebo-controlled trials (subgroup of 18 trials; 7746 subjects). Investigator-reported events suggestive of CHF from 24 placebo-controlled trials (including trials <12 weeks' duration, 8778 subjects) were also analyzed.Results5847 patients received linagliptin (5 mg: 5687, 10 mg: 160) and 3612 comparator (glimepiride: 775, voglibose: 162, placebo: 2675); cumulative exposure, 4421.3 and 3254.7 patient-years, respectively. 4P-MACE incidence rates: 13.4 per 1000 patient-years, linagliptin (60 events), 18.9, total comparators (62 events); overall hazard ratio (HR), 0.78 (95% confidence interval [CI], 0.55-1.12). HR for adjudicated hospitalization for CHF (n = 21): 1.04 (0.43-2.47). For placebo-controlled trials, 4P-MACE incidence rates: 14.9 per 1000 patient-years, linagliptin (43 events), 16.4, total comparators (29 events); overall HR, 1.09 (95% CI, 0.68-1.75). Occurrence of investigator-reported events suggestive of CHF was low for linagliptin- (26 events, 0.5%; serious: 16 events, 0.3%) and placebo-treated (8 events, 0.2%; serious: 6 events, 0.2%) patients.ConclusionsLinagliptin is not associated with increased CV risk versus pooled active comparators or placebo in patients with T2DM.

| S-EPMC4465456 | biostudies-literature

Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study.

Project description:AimsPrevious studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. However, few have been active comparison studies that directly assessed the potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase 2 (COX-2)-selective and nonselective NSAIDs in patients with hypertension.MethodsWe conducted a cohort study of patients with hypertension who initiated COX-2-selective or nonselective NSAIDs in a population-based Taiwanese database. The outcomes included hospitalization for the following major cardiovascular events: ischaemic stroke, acute myocardial infarction, congestive heart failure, transient ischaemic attack, unstable angina or coronary revascularization. We followed patients for up to 4 weeks, based on the as-treated principle. We used inverse probability weighting to control for baseline and time-varying covariates, and estimated the on-treatment hazard ratios (HRs) and 95% conservative confidence interval (CIs).ResultsWe identified 2749 eligible COX-2-selective NSAID users and 52?880 eligible nonselective NSAID users. The HR of major cardiovascular events comparing COX-2-selective with nonselective NSAIDs after adjusting for baseline and time-varying covariates was 1.07 (95% CI 0.65, 1.74). We did not observe a differential risk when comparing celecoxib to diclofenac (HR 1.17; 95% CI 0.61, 2.25), ibuprofen (HR 1.36; 95% CI 0.58, 3.18) or naproxen (HR 0.75; 95% CI 0.23, 2.44). There was an increased risk with COX-2-selective NSAIDs, however, when comparing COX-2-selective NSAIDs with mefenamic acid (HR 2.11; 95% CI 1.09, 4.09).ConclusionsOur results provide important information about the comparative cardiovascular safety of NSAIDs in patients with hypertension.

| S-EPMC5903261 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data