scholarly journals What Is the Mechanism Driving the Reduction of Cardiovascular Events from Glucagon-like Peptide-1 Receptor Agonists?—A Mini Review

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4822
Author(s):  
Jared Berndt ◽  
Soo Liang Ooi ◽  
Sok Cheon Pak
Keyword(s):  
Cardiovascular Events ◽  
Standard Of Care ◽  
The Body ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Patients ◽  
Receptor Agonists ◽  
Wide Range ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Cv Disease

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are considered the standard of care for type 2 diabetes in many countries worldwide. These molecules have profound anti-hyperglycaemic actions with a favourable safety profile. They are now being considered for their robust cardiovascular (CV) protective qualities in diabetic patients. Most recent CV outcome trials have reported that GLP-1 RAs reduce major adverse cardiovascular events (MACE). Furthermore, the GLP-1 RAs seem to target the atherosclerotic CV disease processes preferentially. GLP-1 RAs also improve a wide range of routinely measured surrogate markers associated with CV risk. However, mediation analysis suggests these modest improvements may contribute indirectly to the overall anti-atherogenic profile of the molecules but fall short in accounting for the significant reduction in MACE. This review explores the body of literature to understand the possible mechanisms that contribute to the CV protective profile of GLP-1 RAs.

scholarly journals Glucagon-like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter Inhibitors for Treatment of T2DM

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Alexis McKee ◽  
Ali Al-Khazaali ◽  
Stewart G Albert
Keyword(s):  
Adverse Events ◽  
Relative Rate ◽  
Major Adverse Cardiovascular Events ◽  
Serious Adverse Events ◽  
Similar Reduction ◽  
Renal Outcomes ◽  
Receptor Agonists ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes. Objective Assist in the prescribing decision regarding severity of illness and risk for adverse events. Design Meta-analysis of the major CVOT and previous meta-analyses. Main Outcome Measures Six trials of GLP-1 RA (51 762 subjects) and 4 trials of SGLT2i (33 457 subjects) showed both drug classes reduced MACE and CVD versus controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: relative rate [rr] MACE 1.04, 95% confidence interval [CI] 0.94, 1.16, P = ns; rr CVD 1.04, 95% CI 0.87, 1.24, P = ns). Hospitalization for heart failure (HHF) improved with SGLT2i (rr 0.68, CI 0.61, 0.76, P < 0.001) but not with GLP-1 RA, (rr 0.93, CI 0.86,1.03, P = ns). Meta-regression suggested benefits of the SGLT2i on CVD and HHF were accentuated with the underlying rate of MACE in the cohort (i.e., >10 events/1000pt*year). GLP-1 RA and SGLT2i showed reduction in renal outcomes (GLP-1 RA rr 0.83, CI 0.75, 0.91, p ≤ 0.001, SGLT2i rr 0.67, CI 0.57, 0.79, P < 0.001) without a preferential difference (GLP-1 RA vs SGLT2i, rr 1.24, CI 0.95, 1.61, P = ns; relative difference (rd) 0.005, CI -0.011, 0.021, P = ns). Serious adverse events for SGLT2i were mycotic genital infections in women (number needed to harm [NNH] = 13 and diabetic ketoacidosis NNH = 595. Gastrointestinal intolerance was the serious adverse event in the GLP1-RA class (NNH = 35). Conclusion GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and renal outcomes. SGLT2i have advantages over GLP-1 RA in reduction in HHF.

scholarly journals Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials

2009 ◽  
Vol 160 (6) ◽  
pp. 909-917 ◽  
Author(s):  
Matteo Monami ◽  
Niccolò Marchionni ◽  
Edoardo Mannucci
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Relevant Information ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

ObjectiveThe role of glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes is debated; many recent trials, which were not included in previous meta-analyses, could add relevant information.Design and methodsAll available randomized controlled trials (RCTs), either published or unpublished, performed in type 2 diabetic patients with GLP-1 receptor agonists (exenatide and liraglutide), with a duration>12 weeks were meta-analysed for HbA1c, body mass index, hypoglycaemia and other adverse events.Results and conclusionsA total of 21 RCTs (six of which unpublished), enrolling 5429 and 3053 patients (with GLP-1 receptor agonists and active comparator or placebo respectively), was retrieved and included in the analysis. GLP-1 receptor agonists determine a significant improvement of HbA1c in comparison with placebo (−1.0 (−1.1, −0.8),P<0.001), with a low risk of hypoglycaemia. There is no evidence of increased cardiovascular risk with the use of GLP-1 receptor agonists. GLP-1 receptor agonists, which induce weight loss, are associated with gastrointestinal side effects. GLP-1 receptor agonists are effective in reducing HbA1c and postprandial glucose. In patients failing to sulphonylureas and/or metformin, GLP-1 receptor agonists are similarly effective as insulin. Available data suggest that the efficacy and tolerability of the novel agent, liraglutide, which is adequate for once-a-day administration, are comparable with those of exenatide bis in die.

scholarly journals Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of double-blind, randomized, placebo-controlled clinical trials

2019 ◽  
Author(s):  
Jing Qin ◽  
Li Song
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Events ◽  
Double Blind ◽  
Receptor Agonists ◽  
Risk Of Death ◽  
Fatal Stroke ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fatal Myocardial Infarction

Abstract Background The cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients. Methods PubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke. Results We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P=0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR:0.91; 95% CI: 0.82-1.01; P=0.06). Conclusion We concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes.

Sign in / Sign up

Export Citation Format

Share Document