The postprandial actions of GLP-1 receptor agonists: The missing link for cardiovascular and kidney protection in type 2 diabetes

Thomas, Merlin C; Coughlan, Melinda T.; Cooper, Mark E.

doi:10.1016/j.cmet.2023.01.004

Cited by 30 publications

(14 citation statements)

References 255 publications

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“…Large randomized, placebo-controlled clinical trial of once-weekly semaglutide in diabetic chronic kidney disease patients has been halted based on interim data demonstrating efficacy. and lower reactive oxygen species in the kidneys [14]. Indirect effects include the improvement in glycemic control and weight loss which reduced urinary albumin excretion and eventual impact on the decline in kidney function.…”

Section: Key Pointsmentioning

confidence: 99%

“…These agents also have kidney protective effects through direct and indirect effects. Known direct effects include the beneficial glomerular hemodynamic effects, reduced inflammatory burden, oxidative stress, and lower reactive oxygen species in the kidneys [14]. Indirect effects include the improvement in glycemic control and weight loss which reduced urinary albumin excretion and eventual impact on the decline in kidney function.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

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Emerging evidence for glucagon-like peptide-1 agonists in slowing chronic kidney disease progression

Holliday,

Frost,

Navaneethan

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Diabetic kidney disease continues to increase, and several novel therapeutic agents have been shown to slow the progression of chronic kidney disease in those with diabetes. This review summarizes more recent data on the role of glucagon-like peptide-1 (GLP-1) receptor agonists and kidney outcomes. Recent findings Posthoc analysis of cardiovascular outcome trials, as well as several retrospective studies, demonstrate benefits of GLP-1 receptor agonist therapy for chronic kidney disease progression in diabetics. Although limited randomized clinical trials evidence assessing the effects of GLP-1 receptor agonists on kidney outcomes in diabetic chronic kidney disease patients have been published, FLOW-CKD trial was halted based on interim data for efficacy, and results are awaited. Summary GLP-1 receptor agonism is a promising therapy for slowing the progression of diabetic chronic kidney disease. Recent studies support kidney benefits GLP-1 receptor agonists over insulin and dipeptidyl peptidase-4-inhibitors, and the FLOW-CKD trial would inform the potential benefits for reducing the need for dialysis and kidney-disease related mortality in those with kidney disease.

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Section: Key Pointsmentioning

confidence: 99%

Section: Mechanism Of Actionmentioning

confidence: 99%

Emerging evidence for glucagon-like peptide-1 agonists in slowing chronic kidney disease progression

Holliday,

Frost,

Navaneethan

2024

Current Opinion in Nephrology &Amp; Hypertension

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“…Through altering Nrf2 signals, Tan I has been demonstrated to reduce oxygen consumption and oxidative stress-related cardiomyocyte injury. [88] Additionally, it has been shown to inhibit vascular smooth muscle cell proliferation via insulin-like growth factor 1 receptor/PI3K signal transduction. [89] Tan I can also inhibit the production of vascular endothelial growth factor, cyclin A, and cyclin B, reducing the tumor-activated cell cycle pathway and regulating cell progression in the S phase and G2/M phase.…”

Section: The Specific Mechanism Of Action Of Different Tanmentioning

confidence: 99%

Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review

Li,

Liu,

Shi

et al. 2024

Medicine

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Diabetes mellitus (DM) is one of the most prevalent diseases worldwide, greatly impacting patients’ quality of life. This article reviews the progress in Salvia miltiorrhiza, an ancient Chinese plant, for the treatment of DM and its associated complications. Extensive studies have been conducted on the chemical composition and pharmacological effects of S miltiorrhiza, including its anti-inflammatory and antioxidant activities. It has demonstrated potential in preventing and treating diabetes and its consequences by improving peripheral nerve function and increasing retinal thickness in diabetic individuals. Moreover, S miltiorrhiza has shown effectiveness when used in conjunction with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and statins. The safety and tolerability of S miltiorrhiza have also been thoroughly investigated. Despite the established benefits of managing DM and its complications, further research is needed to determine appropriate usage, dosage, long-term health benefits, and safety.

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“…In contrast, long-acting GLP-1RAs, including liraglutide, dulaglutide, semaglutide, and albiglutide, increase insulin secretion and decrease glucagon secretion, thus lowering fasting and postprandial blood glucose levels ( Davies et al, 2018 ). GLP-1RAs have been demonstrated to offer significant cardiovascular benefits in addition to their glucose-lowering effects ( Thomas et al, 2023 ). They prevent and stabilize ASCVD in both patients with and without T2DM through mechanisms that include not only glucose-lowering and weight-loss but also inhibition of inflammatory factors and adhesion molecules, suppression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, induction of nitric oxide (NO) synthesis in endothelial cells, protection of mitochondrial function and inhibition of oxidative stress, reduction of macrophage inflammation and foam cell formation, and improvement of VSMC dysfunction ( Sposito et al, 2018 ; Saraiva and Franco, 2021 ; Yang et al, 2021 ).…”

Section: Glp-1 and Its Receptorsmentioning

confidence: 99%

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Wang,

Ding,

Cheng

et al. 2024

Front. Pharmacol.

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Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients’ long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells’ synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.

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The postprandial actions of GLP-1 receptor agonists: The missing link for cardiovascular and kidney protection in type 2 diabetes

Cited by 30 publications

References 255 publications

Emerging evidence for glucagon-like peptide-1 agonists in slowing chronic kidney disease progression

Emerging evidence for glucagon-like peptide-1 agonists in slowing chronic kidney disease progression

Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

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