Cardiovascular Outcomes in Trials of Oral Diabetes Medications: A Systematic Review (original) (raw)
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Cardiovascular Outcomes in Trials of Oral Diabetes Medications
2008
Background: A wide variety of oral diabetes medications are currently available for the treatment of type 2 diabetes mellitus, but it is unclear how these agents compare with respect to long-term cardiovascular risk. Our objective was to systematically examine the peerreviewed literature on the cardiovascular risk associated with oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, and meglitinides) for treating adults with type 2 diabetes.
IIUM Medical Journal Malaysia, 2020
Type 2 diabetes mellitus (T2DM) is a major global disease burden that affects millions of people worldwide. The disease is well known to predispose patients to a wide range of macro- and microvascular complications. Cardiovascular complications are common macrovascular consequences among patients with T2DM. The primary goal of T2DM management is to achieve proper glycaemic control that helps to avoid or delay the incidence of disease complications. T2DM management involves the utilisation of oral antidiabetic medications and injectables, including insulin. Hence, we conducted this work to discuss and summarise the cardiovascular outcomes associated with the oral antidiabetic pharmacotherapy prescribed for patients with T2DM. The agents involved were metformin, sulfonylurea, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, alpha-glucosidase inhibitors, and sodium-glucose cotransporter-2 inhibitors. We decided to focus on the findings reported from observational studies publishe...
Cardiovascular safety of non-insulin pharmacotherapy for type 2 diabetes
Cardiovascular diabetology, 2017
Patients with type 2 diabetes mellitus have a twofold increased risk of cardiovascular mortality compared with non-diabetic individuals. There is a growing awareness that glycemic efficacy of anti-diabetic drugs does not necessarily translate to cardiovascular safety. Over the past few years, there has been a number of trials evaluating the cardiovascular effects of anti-diabetic drugs. In this review, we seek to examine the cardiovascular safety of these agents in major published trials. Metformin has with-stood the test of time and remains the initial drug of choice. The sulfonylureas, despite being the oldest oral anti-diabetic drug, has been linked to adverse cardiovascular events and are gradually being out-classed by the various other second-line agents. The glitazones are contraindicated in heart failure. The incretin-based drugs have been at the fore-front of this era of cardiovascular safety trials and their performances have been reassuring, whereas the meglitinides and th...
BMJ open, 2017
Cardiovascular diseases are the leading cause of morbidity and mortality among individuals with diabetes. Despite the beneficial effects of antidiabetic drugs (ADDs) in terms of lowering haemoglobin A1c, several ADDs have been shown to increase the risk of cardiovascular events. Given the high prevalence of cardiovascular disease among individuals with diabetes, it is important to weigh the benefits of ADDs against their cardiovascular safety. Therefore, the objective of the current study is to conduct a systematic review with network meta-analysis to compare the effects of different oral pharmacological classes of ADDs on cardiovascular safety. Randomised clinical trials (RCTs) and observational studies published in English up to 31 January 2017, and which include direct and/or indirect evidence, will be included. Studies will be retrieved by searching four electronic databases and cross-referencing. Dual selection and abstraction of data will occur. The primary outcome will be car...
BMJ, 2007
Objective To review the literature on the association between antidiabetic agents and morbidity and mortality in people with heart failure and diabetes. Design Systematic review and meta-analysis of controlled studies (randomised trials or cohort studies) evaluating antidiabetic agents and outcomes (death and admission to hospital) in patients with heart failure and diabetes. Data sources Electronic databases, manual reference search, and contact with investigators. Review methods Two reviewers independently extracted data. Risk estimates for specific treatments were abstracted and pooled estimates derived by metaanalysis where appropriate. Results Eight studies were included. Three of four studies found that insulin use was associated with increased risk for all cause mortality (odds ratio 1.25, 95% confidence interval 1.03 to 1.51; 3.42, 1.40 to 8.37 in studies that did not adjust for diet and antidiabetic drugs; hazard ratio 1.66, 1.20 to 2.31; 0.96, 0.88 to 1.05 in the studies that did). Metformin was associated with significantly reduced all cause mortality in two studies (hazard ratio 0.86, 0.78 to 0.97) compared with other antidiabetic drugs and insulin; 0.70, 0.54 to 0.91 compared with sulfonylureas); a similar trend was seen in a third. Metformin was not associated with increased hospital admission for any cause or for heart failure specifically. In four studies, use of thiazolidinediones was associated with reduced all cause mortality (pooled odds ratio 0.83, 0.71 to 0.97, I 2 =52%, P=0.02). Thiazolidinediones were associated with increased risk of hospital admission for heart failure (pooled odds ratio 1.13 (1.04 to 1.22), I 2 =0%, P=0.004). The two studies of sulfonylureas had conflicting results, probably because of differences in comparator treatments. Important limitations were noted in all studies. Conclusion Metformin was the only antidiabetic agent not associated with harm in patients with heart failure and diabetes. It was associated with reduced all cause mortality in two of the three studies.
European Journal of Preventive Cardiology
Aims To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naïve patients with type 2 diabetes (T2D). Methods and results A meta-analysis was performed of randomized controlled clinical trials of GLP-1RAs and SGLT-2 inhibitors on T2D populations, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoint, explored in the subgroup of SGLT-2 inhibitors studies, was cardiovascular death or hospitalization for heart failure. A random-effects meta-analysis model was applied. Six eligible trials (three studies of SGLT-2 inhibitors and three trials of GLP-1RAs), including 13 049 patients, were identified and considered eligible for the analyses. The new antidiabetic drugs were associated with a significant reduction in MACE [odds ratio (OR): 0.80, 95% confidence interval: 0.70–0.93...
Acta Diabetologica, 2009
Oral anti-diabetic agents have been associated with adverse cardiovascular events in type 2 diabetes (DM2). We investigated the risk of coronary artery disease (CAD), congestive heart failure (CHF), and mortality using multivariable Cox models in a retrospective cohort of 20,450 DM2 patients from our electronic health record (EHR). We observed no differences in CAD risk among the agents. Metformin was associated with a reduced risk of CHF (HR 0.76, 95% CI 0.64–0.91) and mortality (HR 0.54, 95% CI 0.46–0.64) when compared to sulfonylurea. Pioglitazone was also associated with a lower risk of mortality when compared to sulfonylurea (HR 0.59, 95% CI 0.43–0.81). No other significant differences were found between the oral agents. In conclusions, our results did not identify an increased CAD risk with rosiglitazone in clinical practice. However, the results do reinforce a possible increased risk of adverse events in DM2 patients prescribed sulfonylureas.
HORMONES, 2016
Type 2 diabetes mellitus (T2DM), cardiovascular disease (CvD) and the cardiovascular effect of antidiabetic drugs are today critical medical issues, with the prevalence of T2DM in particular showing a steep increase worldwide, mainly due to unhealthy lifestyle habits. T2DM in association with obesity and other cardiovascular risk factors, results in the development of CvD, the leading cause of morbidity and mortality in patients with T2DM. Thus, treatment of T2DM is an individualized and complex challenge in which targeting cardiovascular risk factors is an important component in the decision making. given the cardiovascular adverse events associated with rosiglitazone, both the food and Drug Administration and the european Medicines Agency currently require the demonstration of cardiovascular safety of new antidiabetic drugs. Consequently, clinical trials to guarantee their cardiovascular safety are now obligatory. This review aims to summarize the available evidence on the cardiovascular effects and safety of the major drugs used in T2DM treatment and also to provide an overview of upcoming and ongoing clinical trials in this field. Our belief is that this review will be of substantial assistance to all medical doctors who are treating diabetic patients, namely primary care physicians, internal medicine doctors, endocrinologists, diabetologists and less well experienced personnel such as young doctors in training.
Cardiovascular diabetology, 2018
Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox...