Cardiovascular Effect of Incretin-Based Therapy in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.
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ABSTRACT: Background
To assess the cardiovascular (CV) risk associated with the use of incretin-based therapy in adult patients with type 2 diabetes mellitus (T2DM) primary prevention group with low CV risks.Methods
The clinical studies on incretin-based therapy published in medical journals until August 2014 were comprehensively searched using MEDLINE, EMBASE and CENTRAL with no language restriction. The studies were systemically reviewed and evaluated for CV risks using a meta-analysis approach and where they meet the following criteria: clinical trial, incidence of predefined CV disease, T2DM with no comorbidities, age > 18 years old, duration of at least 12 weeks, incretin-based therapy compared with other antihyperglycaemic agents or placebo. Statistical analyses were performed using a Mantel-Haenszel (M-H) test. The odds ratios (OR) and their 95% confidence interval (CI) were estimated and displayed for comparison.Results
A total of 75 studies comprising 45,648 patients with T2DM were selected. The pooled estimate demonstrated no significance in decreased CV risk with incretin-based therapy versus control (M-H OR, 0.90; 95% CI, 0.81-1.00).Conclusions
This meta-analysis suggests that incretin-based therapy show no significant protective effect on CV events in T2DM primary prevention group with low CV risks. Prospective randomized controlled trials are required to confirm the results of this analysis.
SUBMITTER: Kim JY
PROVIDER: S-EPMC4831684 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Cardiovascular Effect of Incretin-Based Therapy in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.
Kim Je-Yon JY Yang Seungwon S Lee Jangik I JI Chang Min Jung MJ
PloS one 20160414 4
<h4>Background</h4>To assess the cardiovascular (CV) risk associated with the use of incretin-based therapy in adult patients with type 2 diabetes mellitus (T2DM) primary prevention group with low CV risks.<h4>Methods</h4>The clinical studies on incretin-based therapy published in medical journals until August 2014 were comprehensively searched using MEDLINE, EMBASE and CENTRAL with no language restriction. The studies were systemically reviewed and evaluated for CV risks using a meta-analysis a ...[more]
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Project description:AimTo assess the effects of incretin-based therapies on β-cell function in patients with type 1 diabetes mellitus (T1DM).MethodsWe searched the PubMed, Cochrane Library, Embase, and Web of Knowledge databases for eligible randomized clinical trials published up to July 2021. The inclusion criteria were patients with T1DM or latent autoimmune diabetes in adults, patients treated with dipeptidyl peptidase-4 inhibitors or glucagon like peptide-1 receptor agonists, and outcomes included one of the following: fasting plasma glucose, fasting C-peptide, postprandial C-peptide, C-peptide area under the curve (AUC), homeostasis model assessment for β cell function, and insulin resistance. The effects were analyzed using a random effect model with STATA 11.0.ResultsEight trials including 427 participants were included in the final analysis. A pooled analysis found no significant difference in fasting plasma glucose, fasting C-peptide, postprandial C-peptide, or C-peptide AUC between patients treated with incretin-based therapies and placebo. The two trials that reported changes in 2-hour postprandial C-peptide and two of the four trials that reported changes in C-peptide AUC reported increases after incretin-based therapies.ConclusionThis meta-analysis showed that incretin-based therapies did not preserve β-cell function in patients with T1DM.
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Project description:Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide are incretins secreted from enteroendocrine cells postprandially in part to regulate glucose homeostasis. Dysregulation of these hormones is evident in type 2 diabetes mellitus (T2DM). Two new drugs, exenatide (GLP-1 mimetic) and sitagliptin [dipeptidyl peptidase (DPP) 4 inhibitor], have been approved by regulatory agencies for treating T2DM. Liraglutide (GLP-1 mimetic) and vildagliptin (DPP 4 inhibitor) are expected to arrive on the market soon.The background of incretin-based therapy and selected clinical trials of these four drugs are reviewed. A MEDLINE search was conducted for published articles using the key words incretin, glucose-dependent insulinotropic polypeptide, GLP-1, exendin-4, exenatide, DPP 4, liraglutide, sitagliptin, and vildagliptin.Exenatide and liraglutide are injection based. Three-year follow-up data on exenatide showed a sustained weight loss and glycosylated hemoglobin (HbA(1c)) reduction of 1%. Nausea and vomiting are common. Results from phase 3 studies are pending on liraglutide. Sitagliptin and vildagliptin are orally active. In 24-wk studies, sitagliptin reduces HbA(1c) by 0.6-0.8% as monotherapy, 1.8% as initial combination therapy with metformin, and 0.7% as add-on therapy to metformin. Vildagliptin monotherapy lowered HbA(1c) by 1.0-1.4% after 24 wk. Their major side effects are urinary tract and nasopharyngeal infections and headaches. Exenatide and liraglutide cause weight loss, whereas sitagliptin and vildagliptin do not.The availability of GLP-1 mimetics and DPP 4 inhibitors has increased our armamentarium for treating T2DM. Unresolved issues such as the effects of GLP-1 mimetics and DPP 4 inhibitors on beta-cell mass, the mechanism by which GLP-1 mimetics lowers glucagon levels, and exactly how DPP 4 inhibitors lead to a decline in plasma glucose levels without an increase in insulin secretion, need further research.
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Project description:Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.Eligibility criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes.Data collection and analysis Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. Peto's method was used as the primary approach to pool effect estimates from trials, sensitivity analyses were carried out with other statistical approaches, and meta-regression was applied for six prespecified hypotheses to explore heterogeneity. The GRADE approach was used to rate the quality of evidence.Results 189 randomised controlled trials (n=155 145) were included, all of which were at low to moderate risk of bias; 77 reported no events of death and 112 reported 3888 deaths among 151 614 patients. Meta-analysis of 189 trials showed no difference in all cause mortality between incretin drugs versus control (1925/84 136 v 1963/67 478; odds ratio 0.96, 95% confidence interval 0.90 to 1.02, I2=0%; risk difference 3 fewer events (95% confidence interval 7 fewer to 1 more) per 1000 patients over five years; moderate quality evidence). Results suggested the possibility of a mortality benefit with GLP-1 agonists but not DPP-4 inhibitors, but the subgroup hypothesis had low credibility. Sensitivity analyses showed no important differences in the estimates of effects.Conclusions Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes. Further studies are warranted to examine if the effect differs between GLP-1 agonists versus DPP-4 inhibitors.
| S-EPMC5463186 | biostudies-literature
Project description:ObjectiveTo investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.Eligibility criteriaRandomised and non-randomised controlled clinical trials, prospective or retrospective cohort studies, and case-control studies of treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared with placebo, lifestyle modification, or active anti-diabetic drugs.Data collection and analysisPairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. A modified Cochrane tool for randomised controlled trials and a modified version of the Newcastle-Ottawa scale for observational studies were used to assess bias. We pooled data from randomised controlled trials using Peto odds ratios, and conducted four prespecified subgroup analyses and a post hoc subgroup analysis. Because of variation in outcome measures and forms of data, we describe the results of observational studies without a pooled analysis.Results60 studies (n=353,639), consisting of 55 randomised controlled trials (n=33,350) and five observational studies (three retrospective cohort studies, and two case-control studies; n=320,289) were included. Pooled estimates of 55 randomised controlled trials (at low or moderate risk of bias involving 37 pancreatitis events, raw event rate 0.11%) did not suggest an increased risk of pancreatitis with incretins versus control (odds ratio 1.11, 95% confidence interval 0.57 to 2.17). Estimates by type of incretin suggested similar results (1.05 (0.37 to 2.94) for GLP-1 agonists v control; 1.06 (0.46 to 2.45) for DPP-4 inhibitors v control). Analyses according to the type of control, mode, duration of treatment, and individual incretin agents suggested no differential effect by subgroups, and sensitivity analyses by alternative statistical modelling and effect measures did not show important differences in effect estimates. Three retrospective cohort studies (moderate to high risk of bias, involving 1466 pancreatitis events, raw event rate 0.47%) also did not suggest an increased risk of pancreatitis associated with either exenatide (adjusted odds ratios 0.93 (0.63 to 1.36) in one study and 0.9 (0.6 to 1.5) in another) or sitagliptin (adjusted hazard ratio 1.0, 0.7 to 1.3); a case-control study at moderate risk of bias (1003 cases, 4012 controls) also suggested no significant association (adjusted odds ratio 0.98, 0.69 to 1.38). Another case-control study (1269 cases, 1269 controls) at moderate risk of bias, however, suggested that the use of either exenatide or sitagliptin was associated with significantly increased odds of acute pancreatitis (use within two years v no use, adjusted odds ratio 2.07, 1.36 to 3.13).ConclusionsThe available evidence suggests that the incidence of pancreatitis among patients using incretins is low and that the drugs do not increase the risk of pancreatitis. Current evidence, however, is not definitive, and more carefully designed and conducted observational studies are warranted to definitively establish the extent, if any, of increased risk.
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Project description:BackgroundGlycemic control is vital in the care of type 2 diabetes mellitus (T2DM) and is significantly associated with the incidence of clinical complications. This Bayesian network analysis was conducted with an aim of evaluating the efficacy of scaling and root planning (SRP) and SRP?+?adjuvant treatments in improving glycemic control in chronic periodontitis (CP) and T2DM patients, and to guide clinical practice.MethodsWe searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to 4 May 2018 for randomized controlled trials (RCTs). This was at least three months of the duration of study that involved patients with periodontitis and T2DM without other systemic diseases given SRP. Patients in the control group did not receive treatment or SRP combination with adjuvant therapy. Outcomes were given as HbA1c% and levels fasting plasma glucose (FPG). Random-effects meta-analysis and Bayesian network meta-analysis were conducted to pool RCT data. Cochrane's risk of bias tool was used to assess the risk of bias.ResultsFourteen RCTs were included. Most were unclear or with high risk of bias. Compared to patients who did not receive treatment, patients who received periodontal treatments showed improved HbA1c% level, including SRP (the mean difference (MD) -0.399 95% CrI 0.088 to 0.79), SRP?+?antibiotic (MD 0.62, 95% CrI 0.18 to 1.11), SRP?+?photodynamic therapy (aPDT)?+?doxycycline (Doxy) (MD 1.082 95% CrI 0.13 to 2.077) and SRP?+?laser (MD 0.66 95% CrI 0.1037, 1.33). Among the different treatments, SRP?+?aPDT + Doxy ranked best. Regarding fasting plasma glucose (FPG), SRP did not show advantage over no treatment (MD 4.91 95% CI -?1.95 to 11.78) and SRP with adjuvant treatments were not better than SRP alone (MD -0.28 95% CI -8.66, 8.11).ConclusionThe results of this meta-analysis seem to support that periodontal treatment with aPDT + Doxy possesses the best efficacy in lowering HbA1c% of non-smoking CP without severe T2DM complications. However, longer-term well-executed, multi-center trails are required to corroborate the results.
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Project description:ObjectiveTo quantify the risk of overall and type specific cardiovascular and cerebrovascular diseases as well as venous thromboembolism in women with a history of gestational diabetes mellitus.DesignSystematic review and meta-analyses.Data sourcesPubMed, Embase, and the Cochrane Library from inception to 1 November 2021 and updated on 26 May 2022.Review methodsObservational studies reporting the association between gestational diabetes mellitus and incident cardiovascular and cerebrovascular diseases were eligible. Data, pooled by random effects models, are presented as risk ratios (95% confidence intervals). Certainty of evidence was appraised by the Grading of Recommendations, Assessment, Development, and Evaluations.Results15 studies rated as moderate or serious risk of bias were included. Of 513 324 women with gestational diabetes mellitus, 9507 had cardiovascular and cerebrovascular disease. Of more than eight million control women without gestational diabetes, 78 895 had cardiovascular and cerebrovascular disease. Compared with women without gestational diabetes mellitus, women with a history of gestational diabetes mellitus showed a 45% increased risk of overall cardiovascular and cerebrovascular diseases (risk ratio 1.45, 95% confidence interval 1.36 to 1.53), 72% for cardiovascular diseases (1.72, 1.40 to 2.11), and 40% for cerebrovascular diseases (1.40, 1.29 to 1.51). Women with gestational diabetes mellitus showed increased risks of incident coronary artery diseases (1.40, 1.18 to 1.65), myocardial infarction (1.74, 1.37 to 2.20), heart failure (1.62, 1.29 to 2.05), angina pectoris (2.27, 1.79 to 2.87), cardiovascular procedures (1.87, 1.34 to 2.62), stroke (1.45, 1.29 to 1.63), and ischaemic stroke (1.49, 1.29 to 1.71). The risk of venous thromboembolism was observed to increase by 28% in women with previous gestational diabetes mellitus (1.28, 1.13 to 1.46). Subgroup analyses of cardiovascular and cerebrovascular disease outcomes stratified by study characteristics and adjustments showed significant differences by region (P=0.078), study design (P=0.02), source of data (P=0.005), and study quality (P=0.04), adjustment for smoking (P=0.03), body mass index (P=0.01), and socioeconomic status (P=0.006), and comorbidities (P=0.05). The risk of cardiovascular and cerebrovascular diseases was, however, attenuated but remained significant when restricted to women who did not develop subsequent overt diabetes (all gestational diabetes mellitus: 1.45, 1.33 to 1.59, gestational diabetes mellitus without subsequent diabetes: 1.09, 1.06 to 1.13). Certainty of evidence was judged as low or very low quality.ConclusionsGestational diabetes mellitus is associated with increased risks of overall and type specific cardiovascular and cerebrovascular diseases that cannot be solely attributed to conventional cardiovascular risk factors or subsequent diabetes.
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Project description:BackgroundEarly screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.Methods and findingsWe conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge's g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).ConclusionsOur systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.
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Project description:BackgroundDiabetes mellitus is a chronic burden, with a prevalence that is increasing worldwide. Telemetric interventions have attracted great interest and may provide effective new therapeutic approaches for improving type 2 diabetes mellitus (T2DM) care.ObjectiveThe objective of this study was to analyze the clinical effectiveness of telemetric interventions on glycated hemoglobin A1c (HbA1c) specifically and T2DM management generally in a systematic meta-review.MethodsA systematic literature search was performed in PubMed, CINAHL, Cochrane Library, Web of Science Core Collection, and EMBASE databases from January 2008 to April 2020. Studies that addressed HbA1c, blood pressure, fasting blood glucose, BMI, diabetes-related and health-related quality of life, cost-effectiveness, time savings, and the clinical effectiveness of telemetric interventions were analyzed. In total, 73 randomized controlled trials (RCTs), 10 systematic reviews/meta-analyses, 9 qualitative studies, 2 cohort studies, 2 nonrandomized controlled studies, 2 observational studies, and 1 noncontrolled intervention study were analyzed.ResultsOverall, 1647 citations were identified. After careful screening, 99 studies (n=15,939 patients; n=82,436 patient cases) were selected by two independent reviewers for inclusion in the review. Telemetric interventions were categorized according to communication channels to health care providers: (1) "real-time video" interventions, (2) "real-time audio" interventions, (3) "asynchronous" interventions, and (4) "combined" interventions. To analyze changes in HbA1c, suitable RCTs were pooled and the average was determined. An HbA1c decrease of -1.15% (95% CI -1.84% to -0.45%), yielding an HbA1c value of 6.95% (SD 0.495), was shown in studies using 6-month "real-time video" interventions.ConclusionsTelemetric interventions clearly improve HbA1c values in both the short term and the long term and contribute to the effective management of T2DM. More studies need to be done in greater detail.
| S-EPMC7929744 | biostudies-literature
Project description:IntroductionRegulatory requirements mandate that new drugs for treatment of patients with type 2 diabetes mellitus (T2DM), such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, are evaluated to show that they do not increase cardiovascular (CV) risk.MethodsA systematic review was undertaken to evaluate the association between DPP-4 inhibitor and GLP-1 receptor agonist use and major adverse cardiac events (MACE). The National Institutes of Health Medline database was searched for pooled analyses, meta-analyses, and randomized controlled trials (RCTs) of DPP-4 inhibitors and GLP-1 receptor agonists that included CV endpoints.ResultsThirty-six articles met the inclusion criteria encompassing 11 pooled analyses, 17 meta-analyses, and eight RCTs (including secondary analyses). Over the short term (up to 4 years), patients with T2DM exposed to a DPP-4 inhibitor or GLP-1 receptor agonist were not at increased risk for MACE (or its component endpoints) compared with those who received comparator agents. Two meta-analyses showed a significant reduction in the incidence of MACE associated with DPP-4 inhibitor therapy as a drug class, but this beneficial effect was not observed in other meta-analyses that included large RCT CV outcome studies. In four RCTs that evaluated alogliptin, saxagliptin, sitagliptin, or lixisenatide, there was no overall increased risk for MACE relative to placebo in T2DM patients at high risk for CV events or with established CV disease, although there was an increased rate of hospitalization for heart failure associated with saxagliptin. A fifth RCT showed that liraglutide reduced MACE risk by 13% versus placebo.ConclusionOverall, incretin therapy does not appear to increase risk for MACE in the short term.
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Project description:IntroductionThe burden of non-communicable diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) has drastically increased in developing countries over the years. Although recent evidence points to chronic immune activation to be a significant aspect in the pathogenesis and development of T2DM and CVDs, the exact role of T cells is not fully understood. Therefore, we aim to investigate T cell function and cardio vascular risk in T2DM. In addition, the therapeutic effect of blood glucose-lowering drugs to reverse hyperglycaemia induced T cell dysfunction and myocardial infarction will be reviewed.MethodsThis will be a systematic review and meta-analysis of published studies assessing T cell activation and cardiovascular risk in adults with T2DM. The search strategy will include medical subject headings (MeSH) words for PubMed/MEDLINE database. The search terms will also be adapted to grey literature, Embase and Cochrane Central Register of Controlled Trials electronic databases. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened and data will be extracted. Data extraction will be performed using a pre-piloted structured form. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran's Q statistic and the I2 statistics will be used to analyse statistical heterogeneity between studies. If included studies show substantial level of statistical heterogeneity, a random-effects meta-analysis will be performed using R statistical software.DiscussionsThis review will not require ethical approval, and the findings will be disseminated through peer-reviewed publication and conferences. Although other previous studies have reported deregulated T cell function in hyperglycaemia, the underlying mechanisms remain controversial. However, evidence suggests that T cells may be a key component in the development of T2DM and CVDs as its complication. Furthermore, they are a potential diagnostic and therapeutic target in the management of the disease.Systematic review registrationPROSPERO CRD42018099745.
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