Glucose control independent mechanisms involved in the cardiovascular benefits of glucagon-like peptide-1 receptor agonists

Wu, Qinchao; Li, Daisong; Huang, Chao; Zhang, Guoliang; Wang, Zheng; Liu, Jiane; Yu, Hua; Song, Bingxue; Zhang, Ning; Li, Bing; Chu, Xiangcheng

doi:10.1016/j.biopha.2022.113517

Cited by 11 publications

(4 citation statements)

References 143 publications

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“…The anti-inflammatory associations of GLP-1RA treatment with stabilizing atherosclerosis plaque were also suggested as possible pathways for the observed contribution of treatment with GLP-1RAs in reducing CVD. Treatment with GLP-1RAs may also reduce myocardial apoptosis and oxidative stress, as well as increase myocardial glucose uptake and coronary blood flow . Although BMS increases native GLP-1, and treatment with GLP-1RAs increase GLP-1 analog levels, BMS increases the native GLP-1RAs mainly postprandially.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with GLP-1RAs may also reduce myocardial apoptosis and oxidative stress, as well as increase myocardial glucose uptake and coronary blood flow. 21 , 22 , 23 Although BMS increases native GLP-1, and treatment with GLP-1RAs increase GLP-1 analog levels, BMS increases the native GLP-1RAs mainly postprandially. In addition, several studies showed significantly higher postprandial GLP-1 levels after BMS among patients with sustained weight loss than among patients who regained weight, although fasting GLP-1 levels were similar and sometimes returned to a lower than normal value.…”

Section: Discussionmentioning

confidence: 99%

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Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality

Dicker,

Sagy,

Ramot

et al. 2024

JAMA Netw Open

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ImportanceEvidence regarding the relative effectiveness of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in reducing mortality and major adverse cardiovascular events (MACEs) is limited.ObjectiveTo compare all-cause mortality and nonfatal MACEs associated with BMS vs GLP-1RAs for adults with obesity and diabetes and without known cardiovascular disease.Design, Setting, and ParticipantsThis observational, retrospective cohort study was based on data obtained from the electronic medical records of Clalit Health Services (Clalit), the largest health care organization in Israel. The study included 6070 members aged 24 years or older, who had diabetes and obesity and no prior history of ischemic heart disease, ischemic stroke, or congestive heart failure. Patients who underwent BMS and patients who received GLP-1RAs from January 1, 2008, through December 31, 2021, were matched 1:1 by age, sex, and clinical characteristics. Follow-up ended December 31, 2022.ExposuresInitiation of BMS or GLP-1RAs.Main Outcomes and MeasuresThe primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACEs, assessed by multivariate competing risk models.ResultsThe study included 3035 matched pairs of patients (total, 6070; mean [SD] age, 51.0 [9.5] years; 3938 women [64.9%]), who were followed up for a median of 6.8 years (IQR, 4.1-9.4 years). Among those with a diabetes duration of 10 years or less (2371 pairs), mortality was lower for those who underwent BMS than for those treated with GLP-1RAs (hazard ratio [HR], 0.38; 95% CI, 0.25-0.58). This association became nonsignificant when weight loss during the follow-up period was also included in the model (HR, 0.79; 95% CI, 0.43-1.48). Among patients with a duration of diabetes longer than 10 years (664 pairs), no survival advantage was demonstrated for BMS over GLP-1RA (HR, 0.65; 95% CI, 0.39-1.08). The risk for nonfatal MACEs did not differ between the treatment groups (HR, 0.74; 95% CI, 0.49-1.10 among patients with a diabetes duration of ≤10 years; HR, 1.21; 95% CI, 0.80-1.85 among patients with a diabetes duration of &gt;10 years).Conclusions and RelevanceIn this cohort study, BMS was associated with greater reduced mortality compared with first-generation GLP-1RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss. No differences in the risk for mortality were observed between the treatment modalities among individuals with a longer duration of diabetes, nor in the occurrence of nonfatal MACEs among all patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality

Dicker,

Sagy,

Ramot

et al. 2024

JAMA Netw Open

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“…11,12 It has been reported that GLP-1 RA may play an important role in antioxidant, anti-inflammatory, anti-apoptosis, improvement of mitochondrial function and endothelial dysfunction, inhibition of viscous molecule expression, reactive oxygen generation and inhibition of thrombosis, which may be the potential mechanism of GLP-1 RA for cardiac protection. [13][14][15] However, the potential mechanism of GLP-1 RA in cardiovascular protection has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…According to the latest guidelines published by the American Diabetes Association and the European Association for the Study of Diabetes, GLP‐1 RA are strongly recommended as first‐line treatment for patients with cardiovascular disease and diabetes mellitus 11,12 . It has been reported that GLP‐1 RA may play an important role in antioxidant, anti‐inflammatory, anti‐apoptosis, improvement of mitochondrial function and endothelial dysfunction, inhibition of viscous molecule expression, reactive oxygen generation and inhibition of thrombosis, which may be the potential mechanism of GLP‐1 RA for cardiac protection 13–15 . However, the potential mechanism of GLP‐1 RA in cardiovascular protection has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Effects of once‐weekly glucagon‐like peptide‐1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin‐angiotensin system

Yue

et al. 2023

Diabetes Obesity Metabolism

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AimTo investigate the potential mechanism of once‐weekly glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD).MethodsWe searched both Chinese and English databases for randomized controlled trials related to once‐weekly GLP‐1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP‐1 RA. The underlying mechanism was analysed by network pharmacology.ResultsIn total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non‐fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once‐weekly GLP‐1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low‐density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin‐angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched.ConclusionsOur study suggests that once‐weekly GLP‐1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin‐angiotensin system. However, further research is needed to confirm these findings and determine cause and effect.

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Exploring the Evolving Role of SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Managing Cardiovascular Injury Induced by Obesity: Spotlight on ROS as a Key Mediator

Srour,

Ismail,

Njeim

et al. 2024

Oxidative Stress in Applied Basic Research and Clinical Practice

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Glucose control independent mechanisms involved in the cardiovascular benefits of glucagon-like peptide-1 receptor agonists

Cited by 11 publications

References 143 publications

Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality

Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality

Effects of once‐weekly glucagon‐like peptide‐1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin‐angiotensin system

Exploring the Evolving Role of SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Managing Cardiovascular Injury Induced by Obesity: Spotlight on ROS as a Key Mediator

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