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Revue Medicale de Liege Dec 2018Metformin raises much interest in the fields of gynaecology and obstetrics. This article discusses both the efficacy and safety of metformin in the management of... (Review)
Review
Metformin raises much interest in the fields of gynaecology and obstetrics. This article discusses both the efficacy and safety of metformin in the management of polycystic ovary syndrome as well as in the prevention, treatment and follow-up of gestational diabetes. Recent observational data suggest that metformin may also exert positive effects as adjuvant therapy in some cancers, among which endometrial cancer and breast cancer.
Topics: Breast Neoplasms; Diabetes, Gestational; Endometrial Neoplasms; Female; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome; Pregnancy
PubMed: 30570229
DOI: No ID Found -
BMJ Open Jun 2023Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and bone turnover markers.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
METHODS
Searches were carried out in PubMed, EMBASE, Web of science, Cochrane library, ClinicalTrials.gov from database inception to 26 September 2022. Two review authors assessed trial eligibility in accordance with established inclusion criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB V.2.0). Data analysis was conducted with Stata Statistical Software V.16.0 and Review Manager Software V.5.3.
RESULTS
A total of 15 studies with 3394 participants were identified for the present meta-analysis. Our pooled results indicated that metformin had no statistically significant effects on BMD at lumbar spine (SMD=-0.05, 95% CI=0.19 to 0.09, p=0.47, participants=810; studies=7), at femoral (MD=-0.01 g/cm, 95% CI=-0.04 to 0.01 g/cm, p=0.25, participants=601; studies=3) and at hip (MD=0.01 g/cm, 95% CI=0.02 to 0.03 g/cm, p=0.56, participants=634; studies=4). Metformin did not lead to significant change in osteocalcin, osteoprotegerin and bone alkaline phosphatase. Metformin induced decreases in N-terminal propeptide of type I procollagen (MD=-6.09 µg/L, 95% CI=9.38 to -2.81 µg/L, p=0.0003, participants=2316; studies=7) and C-terminal telopeptide of type I collagen (MD=-55.80 ng/L, 95% CI=97.33 to -14.26 ng/L, p=0.008, participants=2325; studies=7).
CONCLUSION
This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the outcomes should be interpreted with caution due to several limitations.
Topics: Humans; Bone Density; Metformin; Lumbar Vertebrae; Bone Remodeling
PubMed: 37355276
DOI: 10.1136/bmjopen-2023-072904 -
Cells Aug 2023The biguanide drug metformin is widely used in type 2 diabetes mellitus therapy, due to its ability to decrease serum glucose levels, mainly by reducing hepatic...
The biguanide drug metformin is widely used in type 2 diabetes mellitus therapy, due to its ability to decrease serum glucose levels, mainly by reducing hepatic gluconeogenesis and glycogenolysis. A considerable number of studies have shown that metformin, besides its antidiabetic action, can improve other disease states, such as polycystic ovary disease, acute kidney injury, neurological disorders, cognitive impairment and renal damage. In addition, metformin is well known to suppress the growth and progression of different types of cancer cells both in vitro and in vivo. Accordingly, several epidemiological studies suggest that metformin is capable of lowering cancer risk and reducing the rate of cancer deaths among diabetic patients. The antitumoral effects of metformin have been proposed to be mainly mediated by the activation of the AMP-activated protein kinase (AMPK). However, a number of signaling pathways, both dependent and independent of AMPK activation, have been reported to be involved in metformin antitumoral action. Among these, the Wingless and Int signaling pathway have recently been included. Here, we will focus our attention on the main molecular mechanisms involved.
Topics: Female; Humans; Metformin; Wnt Signaling Pathway; AMP-Activated Protein Kinases; Diabetes Mellitus, Type 2; Neoplasms
PubMed: 37681914
DOI: 10.3390/cells12172182 -
Pediatric Endocrinology, Diabetes, and... 2020Metformin is a widely used drug in treating type 2 diabetes and insulin resistance and nowadays scientists are searching for new poten-tial and multiple roles in...
INTRODUCTION
Metformin is a widely used drug in treating type 2 diabetes and insulin resistance and nowadays scientists are searching for new poten-tial and multiple roles in prevention and treatment of carcinogenic processes.
AIM OF THE STUDY
The aim of the study was to compare the impact of normoglycemia and hyperglycemia with doses of metformin on vivacity and prolifer-ation of cancer cell lines (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1, NHDF).
MATERIAL AND METHODS
We designed our experiment using raising glucose environment (40 mM, 100 mM, 150 mM, 300 mM) and we added increasing con-centrations of metformin (5 mM, 10 mM, 20 mM, 30 mM). We incubated cells for 24 h, 48 h, 72 h, 96 h. In order to measure of viabil-ity of cancer cells we use MTT assay - a typical test to mark cytotoxic effects of tested substances.
RESULTS
Analysis indicated that populations of cancer cells in our terms was lowering, the incubation of 24 h and 48 h showed favorable results than 72 h and 96 h. In normoglycemic environment (glucose level about 100 mM) and after added metformin in various concentrations we observed decreasing percentage of vivid cells for all cancer cell lines (MCF-7, MCF-7/DX, A549, CCRF/CEM, THP-1).
CONCLUSIONS
The results of our study showed beneficial effects of metformin on decreasing proliferation of cancer cells. Percentage of vivid popula-tions were lowering and we confirmed anti-cancer effect of this drug.
Topics: Antineoplastic Agents; Cell Line; Cell Proliferation; Diabetes Mellitus, Type 2; Humans; Metformin; Neoplasms
PubMed: 33191721
DOI: 10.5114/pedm.2020.98713 -
IUBMB Life Jul 2017Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose... (Review)
Review
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs. One of the best understood molecular targets of metformin is the mitochondrial complex I. However, given metformin's broad effects on metabolism, it could act on multiple targets. In this review, we summarize current findings in metformin's mechanisms of action regarding its known targets in mitochondria and known effects in cancer cell lines. Then, we introduce endosomal Na /H exchangers and the V-ATPase as new potential targets of metformin's action. Finally, we will discuss the hypothesis that metformin directly acts on endosome/lysosome regulation so as to regulate metabolism and ultimately alleviate type 2 diabetes. © 2017 IUBMB Life, 69(7):459-469, 2017.
Topics: Adenylate Kinase; Autophagy; Endosomes; Humans; Hypoglycemic Agents; Mechanistic Target of Rapamycin Complex 1; Metformin; Neoplasms; Organelles; Sodium-Hydrogen Exchangers
PubMed: 28444922
DOI: 10.1002/iub.1633 -
Frontiers in Public Health 2020Currently, tamoxifen is the only drug approved for reduction of breast cancer risk in premenopausal women. The significant cardiovascular side effects of tamoxifen,... (Review)
Review
Currently, tamoxifen is the only drug approved for reduction of breast cancer risk in premenopausal women. The significant cardiovascular side effects of tamoxifen, coupled with lack of a survival benefit, potential for genotoxicity, and failure to provide a significant risk-reduction for estrogen receptor-negative breast cancer, all contribute to the low acceptance of tamoxifen chemoprevention in premenopausal women at high-risk for breast cancer. While other prevention options exist for postmenopausal women, there is a search for well-tolerated prevention agents that can simultaneously reduce risk of breast cancers, cardiovascular disease, and type-2 diabetes. Metformin is a well-tolerated oral biguanide hypoglycemic agent that is prescribed worldwide to over 120 million individuals with type-2 diabetes. Metformin is inexpensive, safe during pregnancy, and the combination of metformin, healthy lifestyle, and exercise has been shown to be effective in preventing diabetes. There is a growing awareness that prevention drugs and interventions should make the "whole woman healthy." To this end, current efforts have focused on finding low toxicity alternatives, particularly repurposed drugs for chemoprevention of breast cancer, including metformin. Metformin's mechanisms of actions are complex but clearly involve secondary lowering of circulating insulin. Signaling pathways activated by insulin also drive biologically aggressive breast cancer and predict poor survival in women with breast cancer. The mechanistic rationale for metformin chemoprevention is well-supported by the scientific literature. Metformin is cheap, safe during pregnancy, and has the potential to provide heart-healthy breast cancer prevention. On-going primary and secondary prevention trials will provide evidence whether metformin is effective in preventing breast cancer.
Topics: Breast Neoplasms; Female; Humans; Metformin; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Tamoxifen
PubMed: 33194937
DOI: 10.3389/fpubh.2020.509714 -
Current Urology Reports Jun 2017Since epidemiological studies first demonstrated a potential positive effect of metformin in reducing cancer incidence and mortality, there has been an increased... (Review)
Review
PURPOSE OF REVIEW
Since epidemiological studies first demonstrated a potential positive effect of metformin in reducing cancer incidence and mortality, there has been an increased interest in not only better understanding metformin's mechanisms of action but also in exploring its potential anti-cancer effects. In this review, we aim to summarise the current evidence exploring a role for metformin in prostate cancer therapy.
RECENT FINDINGS
Preclinical studies have demonstrated a number of antineoplastic biological effects via a range of molecular mechanisms. Data from retrospective epidemiological studies in prostate cancer has been mixed; however, there are several clinical trials currently underway evaluating metformin's role as an anti-cancer agent. Early studies have shown benefits of metformin to inhibit cancer cell proliferation and improve metabolic syndrome in prostate cancer patients receiving androgen deprivation therapy (ADT). While the body of evidence to support a role for metformin in prostate cancer therapy is rapidly growing, there is still insufficient data from randomised trials, which are currently still ongoing. However, evidence so far suggests metformin could be a useful adjuvant agent, particularly in patients on ADT.
Topics: Androgen Antagonists; Antineoplastic Agents; Humans; Male; Metabolic Syndrome; Metformin; Prostatic Neoplasms; Retrospective Studies
PubMed: 28444639
DOI: 10.1007/s11934-017-0693-8 -
International Journal of Molecular... Sep 2018Metformin (MTF) is a natural compound derived from the legume . It is the first line antidiabetic drug for type 2 diabetes (T2D) treatment. One of its main antidiabetic... (Review)
Review
Metformin (MTF) is a natural compound derived from the legume . It is the first line antidiabetic drug for type 2 diabetes (T2D) treatment. One of its main antidiabetic effects results from the reduction of hepatic glucose release. First scientific evidence for the anticancer effects of MTF was found in animal research, published in 2001, and some years later a retrospective observational study provided evidence that linked MTF to reduced cancer risk in T2D patients. Its pleiotropic anticancer effects were studied in numerous in vitro and in vivo studies at the molecular and cellular level. Although the majority of these studies demonstrated that MTF is associated with certain anticancer properties, clinical studies and trials provided a mixed view on its beneficial anticancer effects. This review emphasizes the pleiotropic effects of MTF and recent progress made in MTF applications in basic, preclinical, and clinical cancer research.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Drug Screening Assays, Antitumor; Gluconeogenesis; Humans; Metformin; Models, Molecular; Neoplasms
PubMed: 30241339
DOI: 10.3390/ijms19102850 -
Frontiers in Endocrinology 2021Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C,... (Review)
Review
Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C, and assays of zika. In the current Covid-19 pandemic, which has rapidly spread throughout the world, 4 observational studies have been published showing reduced mortality among individuals with home metformin use. There are several potential overlapping mechanisms by which metformin may reduce mortality from Covid-19. Metformin's past anti-infectious benefits have been both against the infectious agent directly, as well as by improving the underlying health of the human host. It is unknown if the lower mortality suggested by observational studies in patients infected with Covid-19 who are on home metformin is due to direct activity against the virus itself, improved host substrate, or both.
Topics: Humans; Hypoglycemic Agents; Metformin; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34367059
DOI: 10.3389/fendo.2021.587801 -
Diabetes Care Mar 2021Since the UK Prospective Diabetes Study (UKPDS), metformin has been considered the first-line medication for patients with newly diagnosed type 2 diabetes. Though direct... (Review)
Review
Since the UK Prospective Diabetes Study (UKPDS), metformin has been considered the first-line medication for patients with newly diagnosed type 2 diabetes. Though direct evidence from specific trials is still lacking, several studies have suggested that metformin may protect from diabetes- and nondiabetes-related comorbidities, including cardiovascular, renal, neurological, and neoplastic diseases. In the past few decades, several mechanisms of action have been proposed to explain metformin's protective effects, none being final. It is certain, however, that metformin increases lactate production, concentration, and, possibly, oxidation. Once considered a mere waste product of exercising skeletal muscle or anaerobiosis, lactate is now known to act as a major energy shuttle, redistributed from production sites to where it is needed. Through the direct uptake and oxidation of lactate produced elsewhere, all end organs can be rapidly supplied with fundamental energy, skipping glycolysis and its possible byproducts. Increased lactate production (and consequent oxidation) could therefore be considered a positive mechanism of action of metformin, except when, under specific circumstances, metformin and lactate become excessive, increasing the risk of lactic acidosis. We are proposing that, rather than considering metformin-induced lactate production as dangerous, it could be considered a mechanism through which metformin exerts its possible protective effect on the heart, kidneys, and brain and, to some extent, its antineoplastic action.
Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Prospective Studies
PubMed: 33608326
DOI: 10.2337/dc20-1964