The effects of metformin on simple obesity: a meta-analysis

Hong-Hong, Ning; Le, Jiong; Wang, Qian; Young, Charlotte Aimee; Deng, Bo; Gao, Peng-Xiang; Zhang, Hai-Qiao; Qin, Shu-Lan

doi:10.1007/s12020-018-1717-y

Cited by 23 publications

(12 citation statements)

References 40 publications

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“…In a study of 154 consecutive non-diabetic, overweight/obese individuals, metformin-treated patients had a mean weight loss of 5.8 ± 7.0 kg in contrast to a loss of 0.8 ± 3.5 kg in an untreated group (159). A meta-analysis of 13 studies addressing the effects of metformin on simple obesity showed that metformin is effective in reducing body weight in this population, without inducing hypoglycemia (160). The Diabetes Prevention Program is a clinical trial that randomized 3234 participants with elevated glucose and overweight/obesity, to metformin, intensive lifestyle intervention (ILS), or placebo.…”

Section: Tackling Obesity: the Many Facets Of Weight Lossmentioning

confidence: 99%

The Many Faces of Obesity and Its Influence on Breast Cancer Risk

2019

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Obesity is associated with increased risk of breast and other cancers. However, the complexity of the underlying mechanisms, together with the interplay of diet and physical activity-contributing to energy balance-and the role of adipose tissue, pose challenges to our understanding of the basis of this increased risk. Epidemiologic studies have documented a higher obesity prevalence in US black women compared to white women. Elucidation of the contribution of potential biological differences among racially distinct groups to their differences in breast cancer (BC) risk and mortality have been topics of considerable interest in recent years. The racial and ethnic variation in body fat distribution may account for at least part of the differences in breast cancer rates in these populations. Yet, while black women exhibit higher rates of obesity compared to white women, this does not translate directly into higher rates of BC. In fact, overall, BC in black women occurs with a lower incidence than BC in white women. Obesity is a known risk factor for postmenopausal breast cancer, and growing evidence suggests that abdominal obesity, also known as central obesity, may increase risk for triple negative breast cancer, which is more common in premenopausal women. The positive association of postmenopausal BC risk and specifically estrogen receptor (ER)-positive BC, is presumably due largely to accumulation of estrogen in the adipose tissue of the breast and other tissues. Of the two main types of adipose tissue-subcutaneous and visceral-visceral adipocytes are more active metabolically. Such adipose tissue harbors multiple molecular entities that promote carcinogenesis: endocrine molecules/hormones, immunologic factors, inflammatory cytokines, metabolic alterations, and other components of the microenvironment. Expression of these culpable entities is largely regulated by epigenetic mechanisms. The interrelationship between these entities and drivers of epigenetic alteration are critical to the regulation of pathways connecting obesity and cancer risk. Initiatives to counteract the carcinogenic effects of obesity have primarily involved modulation of energy balance by diet. However, targeting of specific molecular abnormalities characterizing adiposity offers an alternative approach to preventing cancer. Our goal in this review is to first discuss the major mechanisms contributing to the obesity-breast cancer link. We will also consider race, specifically black/white differences, as they relate to the association of obesity with breast cancer risk. Then we will enumerate strategies targeting these mechanisms to reduce BC risk, in large part by way of dietary interventions with potential to mitigate the cancer-promoting components of adiposity.

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Section: Tackling Obesity: the Many Facets Of Weight Lossmentioning

confidence: 99%

The Many Faces of Obesity and Its Influence on Breast Cancer Risk

2019

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“…According to one recent meta-analysis, metformin is operative in reducing body weight of simple obesity (in nondiabetic, non-polycystic ovary syndrome (PCOS) patients), by reducing the absorption of glucose in the intestine, decreasing DOI: http://dx.doi.org/10.5772/intechopen.90465 production of glucose in the liver, and ameliorating insulin sensitivity via increasing muscle glucose uptake and use [15].…”

Section: Health Issuesmentioning

confidence: 99%

Metformin in Health Issues and Reproductive System

Pourmatroud¹

2019

Metformin [Working Title]

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Metformin is one of oldest drug in reproductive medicine era; but most of times it is equal to polycystic ovary (PCO) syndrome especially obese patients. If it is still valuable or not, could have another health benefit or new fertility roles, and could be effective as well in male reproductive system will be discussed. According to increased rate of metabolic disorders and cardiovascular problems and cancers, there are several investigations on this old used drug. Those studies had been magnified its role as "the aspirin of current century," which might have a promising role in longevity of the life. So, the chapter will be interesting.

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“…Metformin is the most widely prescribed oral anti-diabetic drug owing to minimal short and long-term side effects as well as minimal risk of hypoglycemia or weight gain [14,15]. Metformin is also used in the treatment of various other diseases such as obesity [16], infertility, polycystic ovary syndrome (PCOS), and cancers [15]. While insulin and its analogues cause an increased risk in cancers of the pancreas, colo-rectal cancer as well as the breast cancers, metformin has been widely studied for its potential anti-neoplastic efficacy and were linked to decreasing the risk of breast cancer, improving overall survival and sensitizing cancers to conventional chemo- and radiotherapy [4].…”

Section: Introductionmentioning

confidence: 99%

High Glucose Represses the Anti-Proliferative and Pro-Apoptotic Effect of Metformin in Triple Negative Breast Cancer Cells

et al. 2019

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Metformin, the most widely prescribed anti-diabetic drug, is shown to possess anti-cancer potential in treatment of cancers, including breast cancer; decreases breast cancer risk; and improves overall survival. However, reports suggest that higher glucose concentrations may negatively impact the anti-cancer efficacy of metformin. Therefore, we examined the anti-cancer potential of metformin in triple-negative breast cancer cells (TNBCs) exposed to different glucose (25 mM, 5.5 mM and zero glucose/glucose-starved) conditions. Our data indicates that a high glucose (25 mM) concentration (mimicking diabetes) significantly abrogated the effect of metformin on cell proliferation, cell death and cell cycle arrest in addition to loss of efficacy in inhibition of the mTOR pathway, a key metabolic pathway in TNBC cells. The mTOR pathway is activated in TNBCs compared to other subtypes of breast cancer, regulates the synthesis of proteins that are critical for the growth and survival of cancer cells and its activation is correlated to poor outcomes among TNBC patients, while also contributing to metastatic progression and development of resistance to chemotherapy/radiotherapy. Our studies were performed in two different types of TNBCs, MDA-MB-231 cells (mesenchymal stem cell-like (MSL)) and MDA-MB-468 (basal like-1 (BL-1)). Interestingly, lower concentrations of metformin (50, 100, 250, and 500 μM) significantly increased cell proliferation in 25 mM glucose exposed MDA-MB-231 cells, an effect which was not observed in MDA-MB-468 cells, indicating that the effective concentration of metformin when used as anti-cancer drug in TNBCs may have to be determined based on cell type and blood glucose concentration. Our data indicates that metformin treatment was most effective under zero glucose/glucose-starved conditions in MDA-MB-468 with a significant increase in the apoptotic population (62.3 ± 1.5%; p-value < 0.01). Under 5.5 mM glucose conditions in both MDA-MB-231 and MDA-MB-468 cells our data showed reduced viability of 73.56 ± 2.53%; p-value < 0.05 and 70.49 ± 1.68%; p-value < 0.001, respectively, along with a significant increase in apoptotic populations of both cell types. Furthermore, metformin (2 mM) inhibited the mTOR pathway and its downstream components under zero glucose/glucose-starved conditions indicating that using metformin in combination with agents that inhibit the glycolytic pathway should be more beneficial for the treatment of triple-negative breast cancers in diabetic individuals.

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The effects of metformin on simple obesity: a meta-analysis

Abstract: Metformin is effective in reducing body weight of simple obesity patients, and metformin does not induce hypoglycemia as a side effect.

Cited by 23 publications

References 40 publications

The Many Faces of Obesity and Its Influence on Breast Cancer Risk

The Many Faces of Obesity and Its Influence on Breast Cancer Risk

Metformin in Health Issues and Reproductive System

High Glucose Represses the Anti-Proliferative and Pro-Apoptotic Effect of Metformin in Triple Negative Breast Cancer Cells

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