GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

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Term Occurence Count Dictionary
Exenatide 10 endocrinologydiseasesdrugs
Insulin 2 endocrinologydiseasesdrugs
dulaglutide 4 endocrinologydiseasesdrugs
Albiglutide 9 endocrinologydiseasesdrugs
diabetes mellitus 1 endocrinologydiseases
metabolic syndrome 1 endocrinologydiseases
obesity 4 endocrinologydiseases
type 2 diabetes mellitus 1 endocrinologydiseases
Liraglutide 11 endocrinologydiseasesdrugs

Graph of close proximity drug and disease terms (within 200 characters).

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Select Drug Character Offset Drug Term Instance
Albiglutide 12552 homologyResistant10–12 hNo restrictions or dose adjustments requiredLow incidence of anti-drug antibodies Albiglutide [[57]–[59]]Composed of a GLP-1 (7–36) dimer fused to recombinant human albumin95% homologyResistant5 daysNo
Albiglutide 17098 mediates the anti-inflammatory effects of liraglutide observed after intracerebral haemorrhage [[56]]. Albiglutide Albiglutide is a long-acting GLP-1RA, developed by fusing a GLP-1 dimer to recombinant human albumin.
Albiglutide 17109 anti-inflammatory effects of liraglutide observed after intracerebral haemorrhage [[56]].Albiglutide Albiglutide is a long-acting GLP-1RA, developed by fusing a GLP-1 dimer to recombinant human albumin. A single substitution
Albiglutide 17388 cleaved by DPP-4, which results in a longer half-life and allows for weekly administration [[57]]. Albiglutide has 97% homology to the amino acid sequence of GLP-1. It augments glucose-dependent insulin secretion
Albiglutide 17577 glucose-dependent insulin secretion and slows gastric emptying. The initial dose is 30 mg once weekly [[58]]. Albiglutide is a large biochemical entity that does not cross the blood–brain barrier, which may possibly underlie
Albiglutide 37217 with Semaglutide in Subjects with Type 2 Diabetes) and, more recently, albiglutide (HARMONY Outcomes: Albiglutide and cardiovascular outcomes in patients with T2DM and cardiovascular disease) and dulaglutide (REWIND:
Albiglutide 38033 [135]–[138]]EXSCELELIXALEADERSUSTAIN-6HARMONYREWINDGLP-1RAExenatideLixisenatideLiraglutideSemaglutide (SC) Albiglutide DulaglutideN14,75260689340329794639901Inclusion criteriaT2DMWith prior cardiovascular events and/or with
Albiglutide 40062 group: 8.9%HR 0.74; 95% CI 0.58–0.95P < 0.001 for non-inferiority, P = 0.02 for superiority Albiglutide group: 7.1%Placebo group: 9.0%HR 0.78; 95% CI 0.68–0.90P < 0.001 for non-inferiority, P = 0.0006
Albiglutide 49311 coronary, cerebrovascular or peripheral arterial circulation. Patients with severe CKD were excluded. Albiglutide reduced the risk of MACE by 22% (95% CI 10–32%) when added to standard care in patients with T2DM
Exenatide 11575 GLP-1RAsDrugStructure/homology To Human GLP-1DPP-4 cleavageHalf-lifeRecommendations in renal impairmentAntibodies Exenatide [[39], [43]–[45]]Substitution of alanine in position 2 by glycine53% homologyResistant2–4 h (12 h
Exenatide 13878 dipeptidyl peptidase 4; GFR, glomerular filtration rate; GLP-1, glucagon-like peptide-1; Lys, lysine Exenatide Exenatide was designed as a recombinant synthetic form of the peptide exendin-4, and in 2005, was the
Exenatide 13887 dipeptidyl peptidase 4; GFR, glomerular filtration rate; GLP-1, glucagon-like peptide-1; Lys, lysineExenatide Exenatide was designed as a recombinant synthetic form of the peptide exendin-4, and in 2005, was the first GLP-1RA
Exenatide 14097 GLP-1RA to be approved by the US Food and Drug Administration (FDA) for the treatment of T2DM [[43]]. Exenatide was first introduced as a twice-daily injection of 5 mcg for 1 month, followed by 5 mcg or 10 mcg.
Exenatide 14673 vagal-independent pathways that result in the direct activation of GLP-1R in the central nervous system. Exenatide is primarily eliminated by the kidneys via renal filtration and enzymatic degradation in the tubules
Exenatide 23562 functional outcome in a transient middle cerebral artery occlusion stroke in rodent models [[93]]. Exenatide was also shown to attenuate neuroinflammation and ameliorate warfarin-associated haemorrhagic transformation
Exenatide 27704 reduction in intestinal absorption of dietary lipids and enhanced hepatic fatty acid oxidation [[111]]. Exenatide and liraglutide have been reported to be equally effective in lowering postprandial dyslipidaemia, an
Exenatide 31618 ameliorates endothelial dysfunction in T2DM patients with established coronary artery disease [[122]]. Exenatide elicits NO production in endothelial cells through activation of GLP-1R and AMP-activated protein kinase
Exenatide 37985 results.Table 2Characteristics of GLP-1RA trials [[100], [135]–[138]]EXSCELELIXALEADERSUSTAIN-6HARMONYREWINDGLP-1RA Exenatide LixisenatideLiraglutideSemaglutide (SC)AlbiglutideDulaglutideN14,75260689340329794639901Inclusion criteriaT2DMWith
Exenatide 39529 non-fatal MI, non-fatal stroke3-point MACE: cardiovascular death, non-fatal MI, non-fatal strokeResults Exenatide group: 11.4%Placebo group: 12.2%HR 0.91; 95% CI 0.83–1.00P < 0.001 for non-inferiority, P = 0.06
Insulin 27223 coronary artery and carotid artery atherosclerosis independently of traditional risk factors [[109]]. Insulin resistance in the liver and adipose cells, the compensatory hyperinsulinaemia, as well as hyperglycaemia
Insulin 30273 arrhythmias, inflammation, or endothelial dysfunction and may favour a prothrombotic state [[117]]. Insulin resistance increases the risk of cardiovascular disease via a spectrum of mechanisms that include fatty
Liraglutide 12285 mL/min56–60% of patients developed anti-drug antibodies, with no apparent effect on efficacy or safety Liraglutide [[51]–[56]]One amino acid substitution (Lys34Arg) with the addition of a C-16 acyl group (palmitoyl)
Liraglutide 15715 catabolism. No data are available about the nature and potential actions of its metabolites [[50]]. Liraglutide Liraglutide is a long-acting GLP-1 analogue, produced by recombinant DNA technology. It has 97% amino
Liraglutide 15726 catabolism. No data are available about the nature and potential actions of its metabolites [[50]].Liraglutide Liraglutide is a long-acting GLP-1 analogue, produced by recombinant DNA technology. It has 97% amino acid homology
Liraglutide 16030 has an increased half-life as a result of DPP-4 resistance and non-covalent binding to serum albumin. Liraglutide should be initiated at a dose of 0.6 mg/day for 1 week and titrated on a weekly basis to a maximum
Liraglutide 16159 initiated at a dose of 0.6 mg/day for 1 week and titrated on a weekly basis to a maximum of 1.8 mg/day. Liraglutide has been shown to significantly reduce fasting and postprandial glycaemia, as well as HbA1c levels.
Liraglutide 16479 reported in humans with and without T2DM has made liraglutide an attractive treatment option [[52]]. Liraglutide is not excreted via the kidneys, in contrast to GLP-1RAs based on exendin-4; consequently, its metabolism
Liraglutide 16695 metabolism and excretion are mostly unaffected by a decreased glomerular filtration rate (GFR) [[53], [54]]. Liraglutide also crosses the blood–brain barrier and has anti-apoptotic, anti-inflammatory, antioxidant and neuroprotective
Liraglutide 29824 acquire greater relevance for individuals in primary prevention settings, such as 20% of the LEADER ( Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation)
Liraglutide 38006 GLP-1RA trials [[100], [135]–[138]]EXSCELELIXALEADERSUSTAIN-6HARMONYREWINDGLP-1RAExenatideLixisenatide Liraglutide Semaglutide (SC)AlbiglutideDulaglutideN14,75260689340329794639901Inclusion criteriaT2DMWith prior cardiovascular
Liraglutide 39796 group: 13.2%HR 1.02; 95% CI 0.89–1.17P < 0.001 for non-inferiority, P = 0.81 for superiority Liraglutide group: 13.0%Placebo group: 14.9%HR 0.87; 95% CI 0.78–0.97P < 0.001 for non-inferiority, P = 0.01
Liraglutide 56072 conducted to evaluate the effect of GLP-1a on cardiac function. The ongoing clinical trial Effects of Liraglutide in Young Adults with Type 2 Diabetes (LYDIA) is investigating changes in cardiac structure and function
dulaglutide 18581 1.28–1.52% was observed, with a weight loss of 1.40–2.51 kg [[61]]. The larger molecular size of dulaglutide may hinder transport across the blood–brain barrier [[42]]. Cardiovascular benefits are still under
dulaglutide 18753 [[42]]. Cardiovascular benefits are still under investigation [[62]], but initial results have shown that dulaglutide does not increase the risk of major cardiovascular events in T2DM patients [[63]].TaspoglutideTaspoglutide
dulaglutide 37311 Outcomes: Albiglutide and cardiovascular outcomes in patients with T2DM and cardiovascular disease) and dulaglutide (REWIND: Researching cardiovascular Events with a Weekly INcretin in Diabetes). These trials were powered
dulaglutide 50971 deathREWINDThe REWIND trial was designed to evaluate the effect of the addition of once-weekly administered dulaglutide on the standard of care for patients with T2DM in the incidence of cardiovascular events [[147]]. Patients
Select Disease Character Offset Disease Term Instance
diabetes mellitus 40859 agonist; HR, hazard ratio; MACE, major adverse cardiovascular event; SC, subcutaneous; T2DM, type 2 diabetes mellitus EXSCELBefore the EXSCEL trial was completed, the exploratory results from a large uncontrolled study
metabolic syndrome 22422 parameters (triglycerides) and carotid intima media thickness after 18 months in T2DM patients with metabolic syndrome [[85]]. In overweight patients with stable coronary artery disease and T2DM, liraglutide increased heart
obesity 2626 continues, 629 million individuals will have diabetes by 2045 [[1]]. Genetic susceptibility, ageing and obesity are contributing to the increase in T2DM prevalence [[2]]. T2DM is mainly caused by a combination of
obesity 3280 complications are mainly represented by atherosclerotic ndisease. Disturbances of glucose levels caused by obesity -related insulin resistance or impaired insulin secretion cause endothelial and smooth muscle cell dysfunction
obesity 3550 already developed vascular complications by the time they are diagnosed with T2DM. Comorbidities such as obesity , hypertension, and dyslipidaemia are important contributors to the increased risk of cardiovascular
obesity 4601 highly desired, especially if they can offer cardiovascular benefits.The strong link between T2DM and obesity is closely related to an impaired crosstalk between the brain and peripheral organs [[17]]. The “incretin
type 2 diabetes mellitus 40852 receptor agonist; HR, hazard ratio; MACE, major adverse cardiovascular event; SC, subcutaneous; T2DM, type 2 diabetes mellitus EXSCELBefore the EXSCEL trial was completed, the exploratory results from a large uncontrolled study

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