GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin

Ouyang, Jing; Isnard, Stéphane; Lin, John; Fombuena, Brandon; Peng, Xiaorong; Chen, Yaokai; Routy, Jean‐Pierre

doi:10.3389/fendo.2020.581839

Cited by 27 publications

(31 citation statements)

References 112 publications

(152 reference statements)

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“…The association between metformin and GDF15 was strengthened by data showing that metformin prevented weight gain in high fat fed mice, but not in mice lacking GDF15, or lacking its receptor, glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL), or following treatment with a GRAL antagonist; however, GDF15 was not required for the antihyperglycemic effects of metformin ( 83 ). A number of studies have reported a positive correlation between the use of metformin and enhanced levels of GDF15 ( 97 ). Of additional interest and based on a proteomic analysis of the plasma from 240 healthy, disease-free, humans in the age range 22-93 years-old, GDF15 was identified as the protein most positively correlated with chronological age and also known to reduce appetite via an action in the hind-brain ( 82 , 95 ).…”

Section: The Putative Relationship Between Metformin and Agingmentioning

confidence: 99%

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

et al. 2021

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The numerous beneficial health outcomes associated with the use of metformin to treat patients with type 2 diabetes (T2DM), together with data from pre-clinical studies in animals including the nematode, C. elegans, and mice have prompted investigations into whether metformin has therapeutic utility as an anti-aging drug that may also extend lifespan. Indeed, clinical trials, including the MILES (Metformin In Longevity Study) and TAME (Targeting Aging with Metformin), have been designed to assess the potential benefits of metformin as an anti-aging drug. Preliminary analysis of results from MILES indicate that metformin may induce anti-aging transcriptional changes; however it remains controversial as to whether metformin is protective in those subjects free of disease. Furthermore, despite clinical use for over 60 years as an anti-diabetic drug, the cellular mechanisms by which metformin exerts either its actions remain unclear. In this review, we have critically evaluated the literature that has investigated the effects of metformin on aging, healthspan and lifespan in humans as well as other species. In preparing this review, particular attention has been placed on the strength and reproducibility of data and quality of the study protocols with respect to the pharmacokinetic and pharmacodynamic properties of metformin. We conclude that despite data in support of anti-aging benefits, the evidence that metformin increases lifespan remains controversial. However, via its ability to reduce early mortality associated with various diseases, including diabetes, cardiovascular disease, cognitive decline and cancer, metformin can improve healthspan thereby extending the period of life spent in good health. Based on the available evidence we conclude that the beneficial effects of metformin on aging and healthspan are primarily indirect via its effects on cellular metabolism and result from its anti-hyperglycemic action, enhancing insulin sensitivity, reduction of oxidative stress and protective effects on the endothelium and vascular function.

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Section: The Putative Relationship Between Metformin and Agingmentioning

confidence: 99%

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

et al. 2021

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“… 44 , 70 GDF-15 and GFRAL signaling pathways are thus suggested to be an important potential therapeutic target for both cancer cachexia and obesity. 7 , 16 , 42 , 46 , 54 , 71 Thus, both GDF15 and GFRAL signaling through the tyrosine kinase receptor RET 18 , 46 are under investigation in several clinical trials. 43 , 46 (Table 1 )…”

Section: Gdf15 and The Identification Of Its Neuroreceptor Gfralmentioning

confidence: 99%

GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

Ahmed¹,

Isnard²,

Lin³

et al. 2021

J. Cancer

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“…Metformin increases the secretion of GDF-15, which binds exclusively to glial cell-derived neurotrophic factor family receptor alpha-like. This gutbrain cytokine works as a prominent player in reducing food intake and body weight in health and disease, like anorexia nervosa and cancer (35).…”

Section: Metformin Therapy In Obese Children 37mentioning

confidence: 99%

“…Metformin, which is known to inhibit lipogenesis in fat cells, may have a direct effect on lipid profile or may be this effect associated with weight loss. Several studies have shown that total cholesterol levels decreased slightly with metformin treatment (30,(34)(35)(36).…”

Section: Metformin Therapy In Obese Children 37mentioning

confidence: 99%

Efficacy of Metformin Therapy in Obese Children with Insulin Resistance

Atakul¹,

Tuhan²,

Abacı³

et al. 2021

Deu Med J

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Objective: Obesity and insulin resistance is an important problem of general public health as well as pediatric endocrinology due to the disorders it causes. Metformin, a well-known oral antidiabetic, is increasingly being a common choice in treatment of obese and insulin resistant children. In this study, it was aimed to retrospectively evaluate the subjects who used metformin treatment due to insulin resistance and exogenous obesity in our clinic and to assess the effects of metformin on anthropometric and metabolic variables. Materials and Methods:The medical records of the 36 patients, who were started metformin therapy due to obesity and insulin resistance and were followed-up in the Pediatric Endocrinology Department of Dokuz Eylül University Medical Faculty between 2005-2015, were retrospectively evaluated. The anthropometric and metabolic variables of these individuals at the sixth month of treatment were compared with basal values.Results: Statistically significant decrease was detected after six months of metformin treatment in weight SDS (Standard Deviation Score) (mean 2.29 to 1.8), BMI (mean 31.3kg/m 2 to 29.8kg/m 2 ), and BMI SDS (mean 2.2 to 1.9) (p<0.001). A mean reduction of 2.41±1.93kg/m 2 was present in BMI values of study subjects (p<0.001). Statistically significant reductions were found in posttreatment fasting insulin, fasting glucose/insulin ratio, HOMA-IR and Quick index values (p<0.05). Conclusion:Metformin is one of the treatment options in obese adolescents with insulin resistance. In our study, it was observed that improvement in anthropometric measurements and metabolic parameters was achieved without any serious side effects in patients who received metformin treatment.

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GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin

Cited by 27 publications

References 112 publications

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

Efficacy of Metformin Therapy in Obese Children with Insulin Resistance

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