diabetestalk.net

Metformin Acts By

Metformin Wonder Drug

Metformin Wonder Drug

A while back I wrote about why metformin is the number one treatment for Type 2 diabetes. Now new research finds metformin prevents cancer and heart disease and may actually slow aging! Where can I get this stuff? A study from Scotland found that people on metformin had only roughly half the cancer rate of people with diabetes who weren’t on the drug. This is important, because diabetes is associated with higher risks of liver, pancreas, endometrial, colon and rectum, breast, and bladder cancer. Nobody could explain how metformin helped, but then Canadian researchers showed that metformin reduces cell mutations and DNA damage. Since mutations and DNA damage promote both cancer and aging, this is striking news. No one thought we could limit mutations before, but perhaps metformin can do it. A study on mice exposed to cigarette smoke showed that those given metformin had 70% less tumor growth. A small study of humans in Japan showed similar improvements in colorectal cancer outcomes. Metformin is now being studied in clinical trials for breast cancer. The researchers write, “Women with early-stage breast cancer taking metformin for diabetes have higher response rates to [presurgical cancer therapies] than diabetic patients not taking metformin.” They also had better results than people without diabetes. How Does It Work? According to Michael Pollak, MD, professor in McGill’s Medicine and Oncology Departments, metformin is a powerful antioxidant. It slows DNA damage by reducing levels of “reactive oxygen species” (ROS). ROS are produced as byproducts when cells burn glucose. Just as oxygen helps fires burn or metals rust, ROS will oxidize (“burn” or “rust”) the nuclei or other parts of cells. ROS are what the antioxidant vitamins are supposed to block. Continue reading >>

How Metformin Acts In Pcos Pregnant Women

How Metformin Acts In Pcos Pregnant Women

Abstract OBJECTIVE Metformin has been reported to reduce the risk of gestational diabetes (GD) in women with polycystic ovarian syndrome (PCOS). However, little is known about the mechanisms of action of this drug during pregnancy. In the attempt to fill this gap, we performed a prospective longitudinal study providing a detailed examination of glucose and insulin metabolism in pregnant women with PCOS undergoing metformin therapy. RESEARCH DESIGN AND METHODS We enrolled 60 women with PCOS who conceived while undergoing metformin treatment. An oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp were performed at each trimester of gestation in 47 ongoing pregnancies. RESULTS Twenty-two of the study subjects had development of GD despite the treatment. At baseline, insulin sensitivity was comparable between women who had development of GD and women who did not. A progressive decline in this parameter occurred in all subjects, independently of the trimester of GD diagnosis. Insulin secretion was significantly higher during the first trimester in patients with an early failure of metformin treatment. Women with third trimester GD and women with no GD exhibited a significant increase in insulin output as gestation proceeded. All newborns were healthy and only one case of macrosomia was observed. CONCLUSIONS Women with PCOS who enter pregnancy in a condition of severe hyperinsulinemia have development of GD earlier, independently of metformin treatment. The physiologic deterioration of insulin sensitivity is not affected by the drug and does not predict the timing and severity of the glycemic imbalance. Despite the high incidence of GD observed, the drug itself or the intensive monitoring probably accounted for the good neonatal outcome. Continue reading >>

Use Of Metformin In Pregnancy

Use Of Metformin In Pregnancy

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form. Summary Metformin is an antihyperglycaemic biguanide used in the management of type 2 diabetes. It acts by lowering basal and postprandial plasma glucose without stimulating insulin secretion, thereby reducing the risk of hypoglycaemia associated with insulin therapy. Metformin is also used off-label for the treatment of infertility secondary to polycystic ovarian syndrome (PCOS). The available data do not show an increased risk of congenital malformation, spontaneous abortion, preterm delivery, small or large for gestational age infants, perinatal mortality or neonatal complications. However, there are insufficient data relating to metformin exposure in early pregnancy to exclude an increased risk of congenital malformations or spontaneous abortion. NICE guidance states that women with diabetes may be advised to use metformin as an adjunct or alternative to insulin in the preconception period and during pregnancy, when the likely benefits from improved blood glucose control outweigh the potential for harm. Exposure to metformin at any stage of pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring over and above that recommended for women with diabetes in pregnancy. However, other risk factors may be present in individual cases which independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments. This document is reg Continue reading >>

Rxproduct News Profile: Fortamet Er (metformin Hydrochloride)

Rxproduct News Profile: Fortamet Er (metformin Hydrochloride)

Background Type 2 diabetes (formerly known as non?insulin-dependent diabetes or adult-onset diabetes) commonly begins as insulin resistance, with cells using insulin incorrectly. Gradually, the pancreas loses its ability to produce insulin. According to the National Institutes of Health, 18.2 million Americans (6.3% of the US population) have diabetes.1 Type 2 diabetes accounts for ~90% to 95% of all diabetes. This disease is associated with obesity, a family history of diabetes, older age, and physical inactivity. Type 2 diabetes also is more prevalent among African Americans, Hispanic/Latino Americans, American Indians, and some Pacific Islander and Asian Americans. Type 2 diabetes has been treated with several antihyperglycemic drugs. Metformin, used for almost 50 years, has been shown to reduce all-cause and diabetes-related mortality and macrovascular disease risk.2 Fortamet (metformin hydrochloride) Extended-Release (ER) Tablets, marketed by Andrx Laboratories, are a new once-daily formulation. Pharmacology Metformin, a biguanide, acts by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. Fortamet ER uses a single-composition osmotic technology (SCOT), consisting of an osmotically active core formulation surrounded by a semipermeable membrane. Two laser-drilled holes on either side of the tablet enable the drug to exit the tablet at a constant rate.3 Absorption is increased by ~60% when the drug is taken with food. The half-life is approximately 5.4 hours, and ~90% of the drug is renally eliminated within the first 24 hours. Clinical Trials A double-blind, randomized, active?controlled study of a total of 680 patients compared Fortamet ER wit Continue reading >>

The Mechanisms Of Action Of Metformin

The Mechanisms Of Action Of Metformin

Abstract Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome. In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action. More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes. Notes ERP holds a Wellcome Trust Investigator award (102820/Z/13/Z). DGH holds a Wellcome Trust Investigator award (204766/Z/16/Z) and a Cancer Research UK Programme Grant (C37030/A15101). GR acknowledges current funding from the Cunningham Trust. The authors declare that there is no duality of interest associated with this manuscript. All authors were responsible for drafting the article and revising it critically for important intellectual content. All authors approved the version to be published. Continue reading >>

Act Metformin

Act Metformin

How does this medication work? What will it do for me? Metformin belongs to the class of medications called oral hypoglycemics, which are medications that lower blood sugar. It is used to control blood glucose (blood sugar) for people with type 2 diabetes. It is used when diet, exercise, and weight reduction have not been found to lower blood glucose well enough on their own. Metformin works by reducing the amount of glucose made by the liver and by making it easier for glucose to enter into the tissues of the body. Metformin has been found to be especially useful in delaying problems associated with diabetes for overweight people with diabetes. This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here. Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor. Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it. What form(s) does this medication come in? 500 mg Each white-to-off-white, round, film-coated, biconvex tablet with logo on one side and "M" over "M" on the other contains 500 mg of metformin HCl. Nonmedicinal ingredients: crospovidone, magnesium stearate, polyethylene glycol, polyvinyl alcohol, povidone, talc, and titan Continue reading >>

Cellular And Molecular Mechanisms Of Metformin: An Overview

Cellular And Molecular Mechanisms Of Metformin: An Overview

Go to: Introduction Prevalence of type 2 diabetes (T2D) has reached epidemic proportions worldwide and promotes the risk for cardiovascular diseases and early mortality. Prevention and management of T2D has become a major public health challenge around the world. Metformin (1,1-dimethylbiguanide), a biguanide derivate, is the most widely prescribed drug to treat hyperglycemia in individuals with T2D and is recommended, in conjunction with lifestyle modification (diet, weight control and physical activity), as a first line oral therapy along in the recent guidelines of the American Diabetes Association and European Association of the Study of Diabetes [1, 2]. This recommendation was based on clinical studies as the UK Prospective Diabetes Study (UKPDS), a multi-centre randomized controlled trail of different therapies for T2D [3]. This landmark study reported that intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints and death in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks when compared to insulin and sulphonylureas. The reduction of cardiovascular mortality by metformin compared with any other oral diabetes agent or placebo was confirmed by recent meta-analysis including more than 30 clinical trials [4, 5]. Despite being introduced clinically in the 1950s (although it was only available in the United States from 1995), the exact mechanism of action of metformin has not been fully elucidated. Recent clinical trials suggest that metformin, in addition to its efficacy in treating T2D, may also have therapeutic potential in other conditions including diabetic nephropathy, cardiovascular diseases, polycystic ovary disease and the prevention or treatment of cancer. This rev Continue reading >>

Metformin: A Bridge Between Diabetes And Prostate Cancer

Metformin: A Bridge Between Diabetes And Prostate Cancer

Introduction Prostate cancer (PCa) represents one-third of all new cancer cases each year and the second cause of cancer-related death in US (1). Prostate cancer is the stage subsequent to premalignant lesions due to a progressive transition from normal prostatic epithelial cells to prostatic intraepithelial neoplasia. Over time, most tumors evolve in castration-resistant prostate cancer (CRPC) with development of metastasis (2, 3). Advanced stages of the disease and formation of metastasis are the main causes of most PCa-related death. Multiple treatment strategies exist but the survival rates remain low. The current strategies for the management of PCa include surgery, chemotherapy, radiation, and endocrine therapy. In the early stage, PCa is characterized by androgen-dependent growth and medical castration through androgen-deprivation therapy (ADT) is the first-line therapy choice for its treatment. This therapy depresses the proliferative function of androgen receptor (AR) but after 12 and 18 months, patients treated with ADT develop resistance to this therapy (4). In fact, over time, androgen-dependent PCa evolves to androgen-independent PCa and ADT is not useful to treat the progressive stage of PCa. CRPC is the most aggressive form of PCa and it shows resistance to current available therapeutic strategies. Recent studies demonstrated the existence of a relationship between diabetes, insulin levels, and risk of cancer, including PCa, but other studies, investigating the association between diabetes mellitus and PCa, have reported inconsistent findings (5). Notably, although the PCa affects a considerable proportion of men, a reduced incidence of this type of cancer has been observed in subject with type II diabetes mellitus (T2DM). Probably, lower hormone levels, Continue reading >>

Metformin Acts Through Mtorc1

Metformin Acts Through Mtorc1

The evidence for metformin to do anything meaningful to longevity in animal studies is fairly ragged - similar studies show a range of results, none of them spectacular, and many of them too small to be significant. It is a marginal candidate for a drug to slow aging when compared to, say, rapamycin, which has much more robust results in animal studies. Further, the whole business of trying to slightly slow aging by tinkering with the ongoing operation of metabolism, slowing the pace at which the cell and tissue damage that causes aging accumulates, is itself an expensive exercise in achieving marginal results. I have to imagine that the reason the TAME human study of metformin and measures of aging exists is not to achieve useful results, but as a form of pressure on the FDA to start accepting treatments for aging. Since metformin has been approved and widely used for decades, the options for rejecting the trial were limited, and once any such trial has been accepted, the next will be easier to push through the established resistance to considering aging as a condition to be treated. There are a limited number of core mechanisms involved in the link between metabolism and natural variations in longevity, but since all aspects of cellular biochemistry are connected to one another there are any number of ways to influence those core mechanisms. The enormous complexity of molecular biology makes it very hard to map these connections. That work is ongoing now and will be for a long time yet. Thus as a general rule we shouldn't be surprised to learn of newly discovered links between any two of the many approaches demonstrated to modestly slow aging in laboratory species. Here researchers connect metformin with mTOR, the target of rapamycin. mTOR forms two complexes, mTORC1 Continue reading >>

Metformin Revisited

Metformin Revisited

Metformin is the most extensively used oral therapeutic agent for type 2 diabetes mellitus (T2DM). The American Diabetes Association recommends metformin as the first line treatment for T2DM in conjunction with rigorous physical activity and dietary restriction. K Sreekumaran Nair, M.D., Ph.D., with Endocrinology, Diabetes, Metabolism & Nutrition at Mayo Clinic's campus in Rochester, Minnesota, says: "With the rapidly expanding prevalence of T2DM, many novel oral therapeutic agents are emerging, but metformin continues to dominate, both as monotherapy as well as in combination with other medications, including insulin. Metformin can also prevent or delay the onset of T2DM in susceptible populations, such as those with prediabetes, fasting hyperglycemia or impaired glucose tolerance, and it is a safe treatment for pregnant women with gestational diabetes. "In women with polycystic ovarian syndrome, metformin is effective not only at improving insulin sensitivity, but also in enhancing their potential for fertility. Currently, over 150 million people worldwide are using metformin." Metformin is a highly desirable therapy for T2DM for a number of reasons. Haleigh A. James, M.D., an endocrine trainee in Endocrinology, Diabetes, Metabolism & Nutrition at Mayo Clinic's campus in Minnesota, notes: "One of its major advantages is that metformin does not cause significant hypoglycemia. Another advantage is that, unlike hypoglycemic agents such as sulfonylureas or insulin, metformin treatment is not associated with weight gain, but may cause modest weight loss. "Some reports indicate that metformin is associated with preferential fat loss, and it may impart mild anorexic effects via its hypothalamic actions. Although there are conflicting reports, metformin may reduce the risk of Continue reading >>

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

Metformin: An Old But Still The Best Treatment For Type 2 Diabetes

Abstract The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection. Introduction The discovery of metformin began with the synthesis of galegine-like compounds derived from Gallega officinalis, a plant traditionally em Continue reading >>

Metformin

Metformin

Also found in: Dictionary, Thesaurus, Encyclopedia, Wikipedia. metformin [met-for´min] Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved. metformin /met·for·min/ (met-for´min) an antihyperglycemic agent that potentiates the action of insulin, used in the treatment of type 2 diabetes mellitus. metformin a hypoglycemic agent that potentiates the action of insulin, used in treatment of type 2 diabetes mellitus. metformin A biguanide antihyperglycaemic and antidiabetic used for type-2 diabetes, alone or with sulfonurea. Metformin sensitises cells to insulin, decreases serum glucose and insulin, decreases insulin resistance, increases glucose utilisation, decreases triglycerides, and reduces weight; in some patients, it suppresses appetite. Adverse effects GI tract complaints—e.g., diarrhoea, nausea, vomiting, bloating—occur in 30%. Contraindications Metabolic acidosis, liver disease; metformin has an equal and additive effect with troglitazone, which acts by increased peripheral glucose disposal. metformin Glucophage® Diabetology A biguanide antihyperglycemic and antidiabetic used for type 2 DM, alone or with sulfonurea; metformin sensitizes cells to insulin, ↓ serum glucose and insulin, ↓ insulin resistance, ↑ glucose utilization, ↓ TGs, ↓ weight; in some Pts, it suppresses appetite. See Diabetes mellitus. Cf Troglitazone. metformin A biguanide oral HYPOGLYCAEMIC drug used in the treatment of MATURITY ONSET DIABETES. The drug may be dangerous to those with liver or kidney disease or a high alcohol intake. The drug is on the WHO official list. A brand name is Glucophage. metformin biguanide agent used to treat diabetes mellitus; in presen Continue reading >>

The Antidiabetic Drug Metformin Activates The Amp-activated Protein Kinase Cascade Via An Adenine Nucleotide-independent Mechanism

The Antidiabetic Drug Metformin Activates The Amp-activated Protein Kinase Cascade Via An Adenine Nucleotide-independent Mechanism

Metformin, a drug widely used to treat type 2 diabetes, was recently shown to activate the AMP-activated protein kinase (AMPK) in intact cells and in vivo. In this study we addressed the mechanism for this effect. In intact cells, metformin stimulated phosphorylation of the key regulatory site (Thr-172) on the catalytic (α) subunit of AMPK. It did not affect phosphorylation of this site by either of two upstream kinases in cell-free assays, although we were able to detect an increase in upstream kinase activity in extracts of metformin-treated cells. Metformin has been reported to be an inhibitor of complex 1 of the respiratory chain, but we present evidence that activation of AMPK in two different cell types is not a consequence of depletion of cellular energy charge via this mechanism. Whereas we have not established the definitive mechanism by which metformin activates AMPK, our results show that the mechanism is different from that of the existing AMPK-activating agent, 5-aminoimidazole-4-carboxamide (AICA) riboside. Metformin therefore represents a useful new tool to study the consequences of AMPK activation in intact cells and in vivo. Our results also show that AMPK can be activated by mechanisms other than changes in the cellular AMP-to-ATP ratio. Metformin and phenformin are derivatives of guanidine, the active ingredient of French lilac, used to treat diabetes in medieval Europe (1). They were introduced as oral antihyperglycemic agents in the late 1950s, although phenformin was subsequently withdrawn due to problems of lactic acidosis. Metformin, the form used in Europe, was introduced into the U.S. in 1994 and is now very widely used to treat type 2 diabetes. Although its molecular target has been unclear, it promotes insulin-stimulated glucose uptake in mu Continue reading >>

Metformin: Uses, Action, Dosage, Side Effect And Brand Information

Metformin: Uses, Action, Dosage, Side Effect And Brand Information

What is metformin used for? Controlling blood sugar levels in adults, adolescents and children aged 10 years and over with type 2 diabetes. Metformin is used when diet alone has failed to fully control blood sugar. It may be used on its own, in combination with other oral antidiabetic medicines, or with insulin. Polycystic ovary syndrome (PCOS). This is an off-licence use of metformin, so you won't find it mentioned in the information leaflets that come with the medicine. However, metformin is a widely used and established treatment option for this condition. How does metformin work? In type 2 diabetes the cells in the body, particularly muscle, fat and liver cells, become resistant to the action of insulin. Insulin is the main hormone responsible for controlling the level of sugar (glucose) in the blood. It makes cells in the body remove sugar from the blood. When the cells are resistant to insulin this makes blood sugar levels rise too high. Metformin hydrochloride is a type of antidiabetic medicine called a biguanide. It works in a number of ways to lower blood sugar levels in people with type 2 diabetes. Firstly, it increases the sensitivity of muscle cells to insulin. This enables these cells to remove sugar from the blood more effectively. Secondly, it reduces the amount of sugar produced by cells in the liver. Finally, it delays the absorption of sugar from the intestines into the bloodstream after eating so that there is less of a spike in blood sugar levels after meals. Metformin is taken regularly every day to help control blood sugar levels both between and directly after meals. In polycystic ovary syndrome or PCOS many women have high insulin levels, and as a result their cells become resistant to the action of insulin. The high insulin levels also cause an Continue reading >>

Metformin

Metformin

Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes,[4][5] particularly in people who are overweight.[6] It is also used in the treatment of polycystic ovary syndrome.[4] Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes.[7][8] It is not associated with weight gain.[8] It is taken by mouth.[4] Metformin is generally well tolerated.[9] Common side effects include diarrhea, nausea and abdominal pain.[4] It has a low risk of causing low blood sugar.[4] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[10] It should not be used in those with significant liver disease or kidney problems.[4] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[4][11] Metformin is in the biguanide class.[4] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[4] Metformin was discovered in 1922.[12] French physician Jean Sterne began study in humans in the 1950s.[12] It was introduced as a medication in France in 1957 and the United States in 1995.[4][13] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[14] Metformin is believed to be the most widely used medication for diabetes which is taken by mouth.[12] It is available as a generic medication.[4] The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014.[15] In the United States, it costs 5 to 25 USD per month.[4] Medical uses[edit] Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>

More in diabetes