Correction to: GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data.
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SUBMITTER: Sposito AC
PROVIDER: S-EPMC6396451 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Correction to: GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data.
Sposito Andrei C AC Berwanger Otávio O de Carvalho Luiz Sérgio F LSF Saraiva José Francisco Kerr JFK
Cardiovascular diabetology 20190301 1
Following publication of the original article [1], based on the authors review, the GLP1 receptor agonists in type 2 diabetes published in Cardiovascular Diabetology, a meta-analysis of GLP-1 and non-GLP-1 based therapies was performed on cardiovascular outcomes. ...[more]
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Project description:Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.
| S-EPMC6292070 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.
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Project description: Not available
| S-EPMC9485680 | biostudies-literature
Project description:Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are emerging as an important therapy to consider for patients with type 2 diabetes (T2D) given this class of treatment's ability to reduce glycated haemoglobin and their associated weight loss and low risk for hypoglycaemia. Additionally, seven cardiovascular outcomes trials (CVOTs) have been performed in the past 4?years using lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide and oral semaglutide. All have found non-inferiority for cardiovascular outcomes, with many finding superiority of these drugs. These findings have transformed our guidelines on pharmacological treatment of T2D. This review article will discuss GLP-1 RA therapy, review the seven CVOTs reported to date and discuss the implications on current guidelines and therapies going forward.
| S-EPMC7042958 | biostudies-literature
Project description:IntroductionThe impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events during the treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is) for type 2 diabetes is unclear.MethodsWe searched Embase and PubMed. We performed meta-analysis using hazard ratio (HR) and 95% confidence interval (CI) as effect size stratified by drug class on six endpoints of interest, which were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), cardiovascular death (CVD), myocardial infarction (MI), stroke, and all-cause death (ACD). We performed meta-regression to assess the difference between GLP-1RAs and SGLT2is, and the impact of reduction of systolic blood pressure or body weight on reduction of cardiovascular events.ResultsWe included 11 randomized trials. Compared with placebo, SGLT2is reduced HHF by 32% (HR 0.68, 95% CI 0.60-0.76) whereas GLP-1RAs reduced HHF by only 9% (HR 0.91, 95% CI 0.83-0.99). The benefit from SGLT2is on HHF was significantly greater than that from GLP-1RAs (Psubgroup = 0.004). GLP-1RAs reduced stroke by 16% (HR 0.84, 95% CI 0.76-0.93) whereas SGLT2is did not reduce stroke (HR 0.96, 95% CI 0.82-1.12). GLP-1RAs and SGLT2is similarly reduced MACE by 12%, CVD by 15%, MI by 9%, and ACD by 13%. The effects of systolic blood pressure reduction and body weight reduction on the logarithms of HRs of GLP-1RAs or SGLT2is vs. placebo as for reducing six endpoints of interest were not statistically significant (β ranged from - 0.145 to 0.269, and P ranged from 0.211 to 0.941).ConclusionsGLP-1RAs and SGLT2is lead to similar benefits on MACE, CVD, MI, and ACD in adults with type 2 diabetes. The benefit from SGLT2is on HHF is greater than that from GLP-1RAs, while GLP-1RAs vs. placebo significantly reduce stroke whereas SGLT2is do not. The two drug classes reduce cardiovascular events independent of reductions of systolic blood pressure and body weight.
| S-EPMC7509017 | biostudies-literature
Project description:Effects of glucagon-like peptide-1 (GLP-1) receptor agonist on cardiovascular complications of diabetes mellitus (DM) were investigated. In total, 132 DM patients treated in Tengzhou Central People's Hospital from April 2013 to September 2016 were included. Of these, 71 cases treated with basic drugs plus GLP-1 were the research group, and 61 cases treated with glipizide controlled release tablets the control group. The improvement of clinical efficacy of patients in the two groups after treatment was observed. The concentrations of FPG, HbAlc, TC, LDL-C, and HDL-C in serum of patients in the two groups before and after treatment were compared, and the incidence rate of cardiovascular disease complications of diabetes was recorded. Expression of FPG, HbAlc, TC, LDL-C, and HDL-C of patients in the two groups were further detected. ROC curve was drawn to analyze its predictive value. In terms of markedly effective treatment rate and overall effective rate, the research group was significantly better than the control group (P<0.05). After treatment, the concentrations of FPG, HbAlc, TC, LDL-C, and HDL-C in serum of patients in the research group were significantly lower than those in the control group (P<0.05). The incidence rate of cardiovascular diseases and residual vascular risks in the research group were significantly higher than those in the control group (P<0.05). After treatment, the AUC of FPG, HbAlc, TC, LDL-C, and HDL-C in serum for predicting cardiovascular complications in DM patients were, respectively, 0.742, 0.780, 0.737, 0.726, and 0.721. In conclusion, GLP-1 receptor agonist can improve the clinical efficacy of patients. Through ROC curve, FPG, HbAlc, TC, LDL-C and HDL-C can be used as predictors of cardiovascular complications in DM patients, which has high clinical value.
| S-EPMC7027309 | biostudies-literature
Project description:Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk. Accordingly, we encourage the adoption of GLP-1RA plus SGLT2i combination therapy in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (i.e., age ≥ 55 years, overweight/obesity, dyslipidemia, hypertension, current tobacco use, left ventricular hypertrophy, and/or proteinuria). Regarding renal effects, the evidence of SGLT2is in preventing kidney failure is more abundant than for GLP-1RAs, which showed a beneficial effect on albuminuria but not on hard kidney endpoints. Hence, in case of persistent albuminuria and/or uncontrolled metabolic risks (i.e., inadequate glycemic control, hypertension, overweight/obesity) on SGLT2i therapy, GLP-1RAs should be considered as the preferential add-on therapy in T2DM patients with chronic kidney disease. Despite the potential clinical benefits of GLP-1RA plus SGLT2i combination therapy in patients with T2DM, several factors may delay this combination to become a common practice soon, such as reimbursement and costs associated with polypharmacy. Altogether, when administering GLP-1RA plus SGLT2i combination therapy, it is important to adopt an individualized approach to therapy taking into account individual preferences, costs and coverage, toxicity profile, consideration of kidney function and glucose-lowering efficacy, desire for weight loss, and comorbidities.
| S-EPMC10067319 | biostudies-literature
Project description:BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework.Results64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center.ConclusionDulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346.
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Project description:Poorly controlled diabetes is characterized by premature cardiovascular mortality and morbidity. The mechanisms linking hyperglycemia with accelerated atherosclerotic disease have not been fully elucidated; however, are thought to be mediated through vascular inflammation, oxidative stress and endothelial dysfunction. The advent of incretin-based therapy, whether by increasing endogenous glucagon-like peptide (GLP)-1 and glucose-dependent inhibitory polypeptide by inhibition of their breakdown using di-peptidyl peptidase 4 inhibitors, or augmenting GLP-1 activity using either exendin-4-based drugs or synthetic GLP-1 analogs promised not just improvements in glycemic control, but improvements in endothelial function, lipid profiles and markers of vascular inflammation. As such, it was anticipated they would demonstrate cardiovascular benefit in those with diabetes, indeed early meta-analyses suggested cardiovascular events would be reduced. To date, however, this benefit has failed to materialize, indeed the cardiovascular outcome trials, whilst meeting their primary endpoint of cardiovascular safety, have failed to demonstrate any improvements in stroke or myocardial infarction. This review will explore the data and attempt to answer the question: what went wrong?
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