Antioxidative Potentials of Incretin‐Based Medications: A Review of Molecular Mechanisms

Yaribeygi, Habib; Maleki, Mina; Sathyapalan, Thozhukat; Jamialahmadi, Tannaz; Sahebkar, Amirhossein

doi:10.1155/2021/9959320

Cited by 17 publications

(4 citation statements)

References 107 publications

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“…[2][3][4][5][6][7][8] Since their introduction, several different formulations of these antidiabetic agents have been brought to market; to date, seven injectable analogues (twicedaily exenatide immediate-release, once-weekly exenatide extendedrelease, once-daily liraglutide, once-daily lixisenatide, once-weekly albiglutide [currently off-market due to a decline in sales], onceweekly dulaglutide and once-weekly semaglutide) and one orallyadministered analogue (once-daily semaglutide) have been approved by the Food and Drug Administration (FDA). 9 Besides GLP-1 receptor as their putative target, numerous molecular targets have been identified for GLP-1 RAs, [10][11][12][13][14][15][16][17][18][19] which justifies their potential for wider medical applications. In this context, several studies have demonstrated that GLP-1 RAs can alter serum uric acid (SUA) concentration.…”

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confidence: 99%

The effect of glucagon‐like peptide‐1 receptor agonists on serum uric acid concentration: A systematic review and meta‐analysis

Najafi

Bahrami

Butler

et al. 2022

Brit J Clinical Pharma

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Aims Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are a class of medications mainly used for the treatment of type 2 diabetes. They improve glucose tolerance, increase insulin secretion and induce weight loss. There is controversy about the effect of GLP‐1 RAs on serum uric acid (SUA) concentration. Our systematic review aims to objectively answer whether GLP‐1 RAs affect SUA levels. Methods We performed a systematic search on PubMed, Web of Science, Embase, Scopus and Google Scholar datasets up to 27August 2021 with a language restriction of English only. Randomized controlled trials, observational studies, uncontrolled trials and conference abstracts were included. Studies with insufficient data, irrelevant types of study and follow‐up duration of less than a month were excluded from the review. After critical appraisal by the Joanna Briggs Institute checklists, articles underwent data extraction using a prespecified Microsoft Excel sheet. Results Of 1004 identified studies, 17 were eligible for inclusion in this systematic review. Pre‐ to post‐administration analysis of GLP‐1 RA effects on SUA demonstrated that GLP‐1 RAs could significantly reduce SUA concentration (difference in means −0.341, SE 0.063, P value <0.001). However, when compared to placebo, GLP‐1RAs did not perform any better in lowering SUA concentration (difference in means −0.455, SE 0.259, P value 0.079). Surprisingly, the active controls, which included insulin, metformin, sodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors and dipeptidyl‐peptidase 4 inhibitors, did outperform GLP‐1 RAs in reducing SUA concentration (difference in means 0.250, SE 0.038, P value <0.001). Conclusions Administration of GLP‐1 RAs can result in a significant reduction in SUA concentration. However, this reduction is less than that seen with the use of insulin, metformin and SGLT‐2 inhibitors.

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confidence: 99%

The effect of glucagon‐like peptide‐1 receptor agonists on serum uric acid concentration: A systematic review and meta‐analysis

Najafi

Bahrami

Butler

et al. 2022

Brit J Clinical Pharma

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“…For instance, by reducing the generation of ROS, metformin therapy lowers blood glucose levels and oxidative stress [25]. By increasing antioxidant enzymes and lowering inflammatory cytokine levels, incretinbased treatments (e.g., glucagon-like peptide-1 (GLP-1) or dipeptidyl peptidase-4 (DPP-4) inhibitors) have shown antioxidative effects [83]. Exercise has been regularly proven to increase antioxidant capacity, decrease ROS production, and enhance cellular insulin sensitivity [84].…”

Section: Diabetes Therapy and Oxidative Stressmentioning

confidence: 99%

Oxidative Stress Biomarkers in Cystic Fibrosis and Cystic Fibrosis-Related Diabetes in Children: A Literature Review

Pinzaru,

Mihai,

Chisnoiu

et al. 2023

Biomedicines

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The most common inherited condition that results in death, particularly in those of Caucasian heritage, is cystic fibrosis (CF). Of all the young adults diagnosed with cystic fibrosis, 20% will develop hyperglycemia as a complication, later classified as a disease associated with cystic fibrosis. Impaired insulin secretion and glucose intolerance represent the primary mechanisms associated with diabetes (type 1 or type 2) and cystic fibrosis. Oxidative stress represents the imbalance between oxygen-reactive species and antioxidant defense mechanisms. This pathogenic mechanism is vital in triggering other chronic diseases, including cystic fibrosis-related diabetes. It is essential to understand oxidative stress and the significant impact it has on CFRD. This way, therapies can be individually adjusted and tailored to each patient’s needs. This review aims to understand the connection between CFRD and oxidative stress. As a subsidiary element, we analyzed the effects of glycemic balance on complications and their evolution over time, providing insights into their potential benefits in mitigating oxidative stress-associated complications.

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“…GLP-1 mimetics have varying abilities to protect against lipid peroxidation [ 80 ]. These drugs have potent direct and indirect antioxidative capacities (such as antioxidant defense system (ADS) potentiation, prooxidant inhibition, steroid receptor coactivator (SRC) protein suppression, and improvement in mitochondrial function) that enable them to prevent oxidative stress-induced lipid peroxidation [ 21 ]. Patel and colleagues in 2013 reported that GLP-1 therapy prevented lipid peroxidation via improving oxidative stress in mice [ 80 ].…”

Section: Incretins and Lipid Homeostasismentioning

confidence: 99%

The Impact of Incretin-Based Medications on Lipid Metabolism

Yaribeygi

Maleki

Butler

et al. 2021

Journal of Diabetes Research

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Pathophysiological pathways that are induced by chronic hyperglycemia negatively impact lipid metabolism. Thus, diabetes is commonly accompanied by varying degrees of dyslipidemia which is itself a major risk factor for further macro- and microvascular diabetes complications such as atherosclerosis and nephropathy. Therefore, normalizing lipid metabolism is an attractive goal for therapy in patients with diabetes. Incretin-based medications are a novel group of antidiabetic agents with potent hypoglycemic effects. While the impact of incretins on glucose metabolism is clear, recent evidence indicates their positive modulatory roles on various aspects of lipid metabolism. Therefore, incretins may offer additional beneficial effects beyond that of glucose normalization. In the current review, how these antidiabetic medications can regulate lipid homeostasis and the possible cellular pathways involved are discussed, incorporating related clinical evidence about incretin effects on lipid homeostasis.

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Antioxidative Potentials of Incretin‐Based Medications: A Review of Molecular Mechanisms

Cited by 17 publications

References 107 publications

The effect of glucagon‐like peptide‐1 receptor agonists on serum uric acid concentration: A systematic review and meta‐analysis

The effect of glucagon‐like peptide‐1 receptor agonists on serum uric acid concentration: A systematic review and meta‐analysis

Oxidative Stress Biomarkers in Cystic Fibrosis and Cystic Fibrosis-Related Diabetes in Children: A Literature Review

The Impact of Incretin-Based Medications on Lipid Metabolism

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