Oncotarget | Metformin Use Improves Survival Of Diabetic Liver Cancer Patients: Systematic Review And Meta-analysis
Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis Shu-Juan Ma, Yi-Xiang Zheng, Peng-Cheng Zhou, Yan-Ni Xiao, Hong-Zhuan Tan _ Metrics: PDF 672 views | HTML 478 views | ? Shu-Juan Ma1, Yi-Xiang Zheng2, Peng-Cheng Zhou2, Yan-Ni Xiao1 and Hong-Zhuan Tan1 1 Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China 2 Department of Infectious Disease, Viral Hepatitis Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, China Keywords: metformin, liver cancer, survival, diabetes mellitus, meta-analysis Received: May 22, 2016 Accepted: July 19, 2016 Published: August 02, 2016 Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the associa Continue reading >>
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Metformin For Liver Cancer Prevention In Patients With Type 2 Diabetes: A Systematic Review And Meta-analysis
The objective of this study was to review the evidence currently available to examine the potential role of metformin in chemoprevention for liver cancer in patients with type 2 diabetes. A database was developed on the basis of five studies consisting of approximately 105,495 patients with type 2 diabetes. In meta-analyses, metformin was associated with an estimated 62% reduction in the risk of liver cancer among patients with type 2 diabetes (odds ratio 0.38, 95% confidence interval 0.24, 0.59; P < 0.001). The effect estimates were heterogeneous across the five included studies (P for heterogeneity = 0.001; I2 = 78%). When restricting the analysis to the four studies related to hepatocellular carcinoma, metformin was again associated with a significantly lower cancer risk (odds ratio 0.30, 95% confidence interval 0.17, 0.52; P < 0.001), and there was evidence of significant heterogeneity between these four studies (P for heterogeneity = 0.03; I2 = 67%). Metformin appears to be associated with a lower risk of liver cancer in patients with type 2 diabetes. Further investigation, including mechanistic studies, well-designed cohort studies, and possibly controlled trials, is needed. The aims of this study were to evaluate the utility of US-guided FNAB in the diagnostic assessment of nodules with or without clinical/US features suggestive for malignancy and to investigate the additional contribution of BRAF V600E mutation analysis in the detection of differentiated thyroid cancer. Cytology showed high positive predictive value and specificity for the diagnosis of malignant lesions. BRAF V600E mutation was found in 115 samples, 80 of which were also cytologically diagnosed as papillary thyroid cancer. BRAF mutation analysis significantly enhanced the diagnostic value of cyt Continue reading >>
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Mcmaster University Researchers Discover How Metformin Drug Works On Fat In The Liver
How and why metformin needs to interact with insulin to be effective About 120 million people around the world with Type 2 diabetes - and two million in Canada - take the drug metformin to control their disease. While doctors know metformin needs to interact with insulin to be effective, and that it can't lower blood sugar on its own, no one has been able to explain how and why this happens. Researchers at McMaster University are the first to unlock that mystery with their discovery metformin works on fat in the liver. Their research is published in today's issue of the journal Nature Medicine. "The key is that metformin doesn't work to lower blood glucose by directly working on the glucose. It works on reducing harmful fat molecules in the liver, which then allows insulin to work better and lower blood sugar levels," said Greg Steinberg, associate professor in the Department of Medicine of the Michael G. DeGroote School of Medicine. He also holds the Canada Research Chair in Metabolism and Obesity and is a co-director of the Metabolism and Childhood (MAC)-Obesity Research Program. His research team included scientists in Alberta, Australia and Scotland. Steinberg said that most people taking metformin have a fatty liver, which is frequently caused by obesity. "Fat is likely a key trigger for pre-diabetes, causing blood sugar to start going up because insulin can't work as efficiently to stop sugar coming from the liver." In their detective work to uncover what causes fatty liver, the scientists studied mice that have a "genetic disruption" to a single amino acid in two proteins called acetyl-CoA carboxylase (ACC). These proteins, which are controlled by the metabolic sensor AMP-activated protein kinase, regulate fat production as well as the ability to burn fat. Mice w Continue reading >>
Metformin (glucophage) Side Effects & Complications
The fascinating compound called metformin was discovered nearly a century ago. Scientists realized that it could lower blood sugar in an animal model (rabbits) as early as 1929, but it wasn’t until the late 1950s that a French researcher came up with the name Glucophage (roughly translated as glucose eater). The FDA gave metformin (Glucophage) the green light for the treatment of type 2 diabetes in 1994, 36 years after it had been approved for this use in Britain. Uses of Generic Metformin: Glucophage lost its patent protection in the U.S. in 2002 and now most prescriptions are filled with generic metformin. This drug is recognized as a first line treatment to control blood sugar by improving the cells’ response to insulin and reducing the amount of sugar that the liver makes. Unlike some other oral diabetes drugs, it doesn’t lead to weight gain and may even help people get their weight under control. Starting early in 2000, sales of metformin (Glucophage) were challenged by a new class of diabetes drugs. First Avandia and then Actos challenged metformin for leadership in diabetes treatment. Avandia later lost its luster because it was linked to heart attacks and strokes. Sales of this drug are now miniscule because of tight FDA regulations. Actos is coming under increasing scrutiny as well. The drug has been banned in France and Germany because of a link to bladder cancer. The FDA has also required Actos to carry its strictest black box warning about an increased risk of congestive heart failure brought on by the drug. Newer diabetes drugs like liraglutide (Victoza), saxagliptin (Onglyza) and sitagliptin (Januvia) have become very successful. But metformin remains a mainstay of diabetes treatment. It is prescribed on its own or sometimes combined with the newer d Continue reading >>
Original Research Use Of Metformin And Risk Of Kidney Cancer In Patients With Type 2 Diabetes
Highlights • The reimbursement database of the National Health Insurance of Taiwan was used. • Kidney cancer risk was analyzed in users and non-users of metformin. • Metformin reduces the risk of kidney cancer in a dose–response pattern. • The adjusted hazard ratio (95% confidence interval) was 0.279 (0.254–0.307). • Risk of any cancer was also significantly reduced in metformin users. Abstract The anticancer effect of metformin has been reported in the literature but requires additional confirmation in epidemiologic studies. With respect to kidney cancer scarce data are available. This study investigates whether metformin use in patients with type 2 diabetes mellitus (T2DM) might affect kidney cancer risk. The reimbursement database of the National Health Insurance in Taiwan was used. T2DM patients aged ≥40 years and newly treated with either metformin (n = 171,753, “ever users of metformin”) or other antidiabetic drugs (n = 75,499, “never users of metformin”) within 1998–2002 were followed for at least 6 months for kidney cancer until 31 December 2009. The treatment effect was estimated by Cox regression using propensity score weighting by inverse probability of treatment weighting approach. Hazard ratios were estimated for ever versus never users, and for tertiles of cumulative duration of metformin therapy. During follow-up, 917 ever users and 824 never users developed kidney cancer, with respective incidence of 80.09 and 190.30 per 100,000 person-years. The hazard ratio (95% confidence intervals) for ever versus never users is 0.279 (0.254–0.307); and is 0.598 (0.535–0.668), 0.279 (0.243–0.321) and 0.104 (0.088–0.124), respectively, for the first, second, and third tertile of cumulative duration of <14.5, 14.5–45.8 and >45.8 mont Continue reading >>
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- Metformin Improves Overall Survival of Colorectal Cancer Patients with Diabetes: A Meta-Analysis
Risk Of Cancer In Diabetes: The Effect Of Metformin
Risk of Cancer in Diabetes: The Effect of Metformin Endocrine Research Center (Firouzgar), Institute of Endocrinology and Metabolism, Tehran University of Medical Sciences, Tehran 15937-48711, Iran Received 20 July 2013; Accepted 16 August 2013 Academic Editors: A. Kautzky-Willer and N. Tentolouris Copyright © 2013 Mojtaba Malek et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials spec Continue reading >>
Metformin, The Liver, And Diabetes
Most people think diabetes comes from pancreas damage, due to autoimmune problems or insulin resistance. But for many people diagnosed “Type 2,” the big problems are in the liver. What are these problems, and what can we do about them? First, some basic physiology you may already know. The liver is one of the most complicated organs in the body, and possibly the least understood. It plays a huge role in handling sugars and starches, making sure our bodies have enough fuel to function. When there’s a lot of sugar in the system, it stores some of the excess in a storage form of carbohydrate called glycogen. When blood sugar levels get low, as in times of hunger or at night, it converts some of the glycogen to glucose and makes it available for the body to use. Easy to say, but how does the liver know what to do and when to do it? Scientists have found a “molecular switch” called CRTC2 that controls this process. When the CRTC2 switch is on, the liver pours sugar into the system. When there’s enough sugar circulating, CRTC2 should be turned off. The turnoff signal is thought to be insulin. This may be an oversimplification, though. According to Salk Institute researchers quoted on RxPG news, “In many patients with type II diabetes, CRTC2 no longer responds to rising insulin levels, and as a result, the liver acts like a sugar factory on overtime, churning out glucose [day and night], even when blood sugar levels are high.” Because of this, the “average” person with Type 2 diabetes has three times the normal rate of glucose production by the liver, according to a Diabetes Care article. Diabetes Self-Management reader Jim Snell brought the whole “leaky liver” phenomenon to my attention. He has frequently posted here about his own struggles with soarin Continue reading >>
Diabetes: How Do I Help Protect My Liver?
If I have diabetes, is there anything special I need to do to take care of my liver? Answers from M. Regina Castro, M.D. You're wise to wonder about steps to protect your liver. Diabetes raises your risk of nonalcoholic fatty liver disease, a condition in which excess fat builds up in your liver even if you drink little or no alcohol. This condition occurs in at least half of those with type 2 diabetes. It isn't clear whether the condition appears more often in people with type 1 diabetes than in the general population because obesity, which is a risk factor, occurs with similar frequency in both groups. Other medical conditions, such as high cholesterol and high blood pressure, also raise your risk of nonalcoholic fatty liver disease. Fatty liver disease itself usually causes no symptoms. But it raises your risk of developing liver inflammation or scarring (cirrhosis). It's also linked to an increased risk of liver cancer, heart disease and kidney disease. Fatty liver disease may even play a role in the development of type 2 diabetes. Once you have both conditions, poorly managed type 2 diabetes can make fatty liver disease worse. Your best defense against fatty liver disease includes these strategies: Work with your health care team to achieve good control of your blood sugar. Lose weight if you need to, and try to maintain a healthy weight. Take steps to reduce high blood pressure. Keep your low-density lipoprotein (LDL, or "bad") cholesterol and triglycerides — a type of blood fat — within recommended limits. Don't drink too much alcohol. If you have diabetes, your doctor may recommend an ultrasound examination of your liver when you're first diagnosed and regular follow-up blood tests to monitor your liver function. Continue reading >>
Liver Cancer And Diabetes
Relative risks for cancers among people with diabetes are highest for cancers of the liver and the pancreas. Most of the evidence is based on people with type 2 diabetes and there are limited data on risk of HCC among people with type 1 diabetes. A systematic review and meta-analysis of 25 cohort studies published in 2012 reported that diabetes was associated with an increased HCC incidence and mortality compared to people without diabetes in 18 studies giving summary relative risks of 2.01 (95% CI: 1.61-2.51) for incidence and 1.56 (1.30-1.87) for mortality[1]. There was statistically significant heterogeneity among studies for incidence (but not mortality) estimates and the excess risk associated with diabetes appeared to be independent of the potential confounding or common risk factors of geographic location, alcohol consumption, history of cirrhosis, or hepatitis B or hepatitis C virus infection status. The authors found no evidence of publication bias. Evidence for reverse causality or detection bias in the association between diabetes and liver cancer has been identified from studies that have shown that relative risks of HCC among people with diabetes are particularly high soon after diagnosis of diabetes[2][3]. One small study from the United States has suggested that metastatic disease is more common at presentation of liver cancer among people with diabetes than those without diabetes[4]. Possible Mechanisms The higher risk of HCC among people with diabetes could potentially be related to exposure of the liver to high insulin concentrations in the portal circulation that are particularly elevated among people with insulin resistance and type 2 diabetes, particularly if the tumour cells remain sensitive to insulin. Hyperinsulinaemia could increase risk of HCC Continue reading >>
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Side Effects Of Metformin: What You Should Know
Metformin is a prescription drug used to treat type 2 diabetes. It belongs to a class of medications called biguanides. People with type 2 diabetes have blood sugar (glucose) levels that rise higher than normal. Metformin doesn’t cure diabetes. Instead, it helps lower your blood sugar levels to a safe range. Metformin needs to be taken long-term. This may make you wonder what side effects it can cause. Metformin can cause mild and serious side effects, which are the same in men and women. Here’s what you need to know about these side effects and when you should call your doctor. Find out: Can metformin be used to treat type 1 diabetes? » Metformin causes some common side effects. These can occur when you first start taking metformin, but usually go away over time. Tell your doctor if any of these symptoms are severe or cause a problem for you. The more common side effects of metformin include: heartburn stomach pain nausea or vomiting bloating gas diarrhea constipation weight loss headache unpleasant metallic taste in mouth Lactic acidosis The most serious side effect metformin can cause is lactic acidosis. In fact, metformin has a boxed warning about this risk. A boxed warning is the most severe warning from the Food and Drug Administration (FDA). Lactic acidosis is a rare but serious problem that can occur due to a buildup of metformin in your body. It’s a medical emergency that must be treated right away in the hospital. See Precautions for factors that raise your risk of lactic acidosis. Call your doctor right away if you have any of the following symptoms of lactic acidosis. If you have trouble breathing, call 911 right away or go to the nearest emergency room. extreme tiredness weakness decreased appetite nausea vomiting trouble breathing dizziness lighthea Continue reading >>
Meta-analysis Of Studies Using Metformin As A Reducer For Liver Cancer Risk In Diabetic Patients
Liver cancer is the fifth most common cancer worldwide and the third-leading cause of cancer related-death. [1] Diabetes mellitus (DM) is becoming an established independent risk factor for liver cancer as reported in multiple observational studies and subsequent meta-analyses. [2,3] In these existing studies, DM has been reported to confer a 2- to 4-fold risk of liver cancer, and the risk increases with DM severity and duration. However, this risk may be mitigated by antidiabetic medications (ADMs). Metformin, a widely used ADM, has recently attracted great attention for antitumor effect in a wide range of malignancies including liver cancer, through both insulin-dependent and insulin-independent mechanisms. [4] However, the evidence for a cancer preventive effect for metformin has not been consistently demonstrated. Association of metformin and risk of liver cancer are mainly studied in animal and observational human studies. A meta-analysis demonstrated that metformin appeared to have a direct antihepatocellular carcinoma (HCC) effect in animal models. [5] Accumulating epidemiologic studies comparing the risk of liver cancer between those using metformin with those using other ADMs have shown somewhat variable results, [69] and it was also endorsed that confounders were not well addressed in most studies. [2] Several meta-analyses have been published to determine if a consistent effect of metformin use on liver cancer incidence was evident. [1013] Except for the incomplete included studies, meta-analyses in previous reviews were rough, and the heterogeneity was not explored in detail. In our opinion, the differences in estimates and the heterogeneity between studies could largely be explained by differences in study designs, quality, population, the comparators used Continue reading >>
Metformin For Liver Cancer Prevention In Patients With Type 2 Diabetes: A Systematic Review And Meta-analysis
Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis Departments of Epidemiology and Biostatistics (Z.-J.Zha., Z.-J.Zhe.), Shanghai 200025, China Address all correspondence and requests for reprints to: Zhi-Jiang Zhang, M.D., Ph.D., Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, China Search for other works by this author on: Departments of Epidemiology and Biostatistics (Z.-J.Zha., Z.-J.Zhe.), Shanghai 200025, China Search for other works by this author on: Preventive Medicine (R.S.), School of Public Health, Shanghai Jiao Tong University, Shanghai 200025, China Search for other works by this author on: Department of Endocrinology (Q.S.), Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China Search for other works by this author on: Department of Epidemiology (Q.J.), School of Public Health, Fudan University, Shanghai 200032, China Search for other works by this author on: College of Nursing (K.E.K.), University of South Florida, Tampa, Florida 33612 Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 7, 1 July 2012, Pages 23472353, Zhi-Jiang Zhang, Zhi-Jie Zheng, Rong Shi, Qing Su, Qingwu Jiang, Kevin E. Kip; Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 7, 1 July 2012, Pages 23472353, Data on the potential effect of metformin on the risk of liver cancer are limited and inconsistent. The objective of this study was to review the evidence currently available to examine the potential role of metformin in chemo Continue reading >>
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Glyburide And Metformin
Brand Names: US Glucovance Rarely, metformin may cause an acid health problem in the blood (lactic acidosis). The risk of lactic acidosis is higher in people with kidney problems and in people who take certain other drugs like topiramate. The risk is also higher in people with liver problems or heart failure, in older people (65 or older), or with alcohol use. If lactic acidosis happens, it can lead to other health problems and can be deadly. Lab tests to check the kidneys may be done while taking this drug. Talk with the doctor. Call your doctor right away if you have signs of too much lactic acid in the blood (lactic acidosis) like fast breathing, fast or slow heartbeat, a heartbeat that does not feel normal, very bad upset stomach or throwing up, feeling very sleepy, shortness of breath, feeling very tired or weak, very bad dizziness, feeling cold, or muscle pain or cramps. Do not take this drug if you have a very bad infection, low oxygen, or a lot of fluid loss (dehydration). Talk with your doctor before you drink alcohol. If you are having an exam or test with contrast or have had one within the past 48 hours, talk with your doctor. Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. What is this drug used for? It is used to lower blood sugar in patients with high blood sugar (diabetes). What do I need to tell my doctor BEFORE I take this drug? If you have an allergy to glyburide, metformin, or any other part of this drug. If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other Continue reading >>
Can A Diabetes Drug Prevent Cancer Death?
With its near-perfect safety record, low cost, and favorable side-effect profile, the anti-diabetic drug metformin is one of the few FDA-approved drugs Life Extension® recommends its members should take every day. Between 1990 and 2011 alone,1 over 1,000 published studies have yielded confirmatory data on its numerous anti-aging properties, from weight loss and glucose control to cardiovascular disease and cancer defense. As the medical establishment continues to ignore this mounting body of evidence, ongoing research powerfully validates our position. In one of the largest studies of its kind, a team of scientists analyzed cancer risk among 8,000 diabetics treated with metformin.2 Over a 10-year period, they observed a 54% lower incidence of all cancers compared to the general population. Metformin not only exerted a major protective effect against cancer development, but those who developed cancer exhibited a significantly higher survival rate, including those with malignant cancers of the lung, colon, and breast. Of equal significance was the finding that the earlier the metformin regimen was initiated, the greater the preventive benefit. Given that diabetics are predisposed to a horrifically wide array of cancers—of the breast, colon, liver, pancreas, kidney, endometrium (uterine lining), among others3-5—these results have profound implications for all maturing individuals. In this article, the most recent data supporting metformin’s anti-cancer mechanisms are detailed. You will learn of its specific mechanisms of action, which shed further light on the link between obesity, diabetes, and cancer initiation. You will also discover how metformin induces cancer cell death at their earliest stages of development via metabolic pathways that also promote weight los Continue reading >>
Liver Cancer And Diabetes
Liver cancer affects 4,000 people annually Liver cancer is a rare type of cancer that affects one of the most complex organs in the human body. Cases of liver cancer in the UK are far and few between but certain people, including those diagnosed with diabetes, face a higher risk of developing the cancer than the general population. As with other forms of cancer, however, many cases of liver cancer can be prevented by keeping healthy lifestyle habits such as eating healthily, keeping fit and quitting or avoiding smoking. Liver cancer is a general term that refers to either: Primary liver cancer - cancer that originates in the liver Secondary liver cancer - cancer that spreads to the liver from another part of the body, such as the bowel Located below the right lung, your liver is the largest internal organ of the human body and one that performs hundreds of important functions, including producing and releasing glucose when the body the needs it, converting fats to energy when needed and removing toxins from the body. Damage to the liver , which is a common problem for people with diabetes, can disrupt these functions and cause them to fail altogether (liver failure) if left untreated. In the UK, nearly 4,000 people are diagnosed with a form of liver cancer each year. The majority of these are secondary liver cancer - primary liver cancer is rare in the UK, but a common problem in other parts of the world. More men are affected than women (60% versus 40%) and cases tend to develop in older adults over the age of 65. The exact cause of liver cancer is unclear, but the disease is strongly linked to damage, inflammation and scarring of the liver, a condition known as cirrhosis. Common causes of cirrhosis include alcohol misuse, viral infections such as hepatitis B or hep Continue reading >>
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