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Metformin Hcl (glucophage) For Diabetes: Side Effects, Dosage, Mechanism Of Action

Metformin Hcl (glucophage) For Diabetes: Side Effects, Dosage, Mechanism Of Action

Metformin has been used for over 40 years and is the most frequently prescribed medication for type 2 diabetes. Metformin is a first-line medication prescribed to help patients control their blood sugars. The American Diabetes Association states that type 2 diabetes treatment should begin with metformin and lifestyle interventions. When used in conjunction with a proper diet and exercise program or with other medications patients can see positive benefits. Controlling high blood sugar can prevent kidney damage, blindness, nerve problems, amputations, and can decrease the risk of a heart attack or stroke. In a landmark study called United Kingdom Prospective Diabetes Study (UKPDS) people treated with metformin had risk reductions of 32% for any diabetes-related problem, 42% for diabetes-related death, and 36% for death from any cause. These results were significantly better than the control group and other treatments did not perform as well as metformin. Here is a summary of important information about metformin. Brand Name: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet Generic Name: metformin hydrochloride Medication Class: Biguanides Similar Drugs: None. Metformin’s mechanism of action is different from other classes of diabetes medications. Manufactured by: Bristol-Myers Squibb, Teva Pharmaceuticals, Mylan Laboratories, Goldline Pharmaceuticals FDA Approval Date: December 1994 What is metformin and how does it work? In the United States, approximately 5% of the people diagnosed with diabetes have type 1 diabetes (about 1 million) and approximately 90-95% has type 2 diabetes. Metformin is an oral medication that lowers blood glucose (sugar) and is effective in treating type 2 diabetes. Insulin is an important hormone produced by the pancreas and it controls g Continue reading >>

Metformin: From Mechanisms Of Action To Therapies

Metformin: From Mechanisms Of Action To Therapies

View all Images/DataFigure 1 Metformin is transported into hepatocytes mainly through OCT1 and partially inhibits mitochondrial respiratory-chain complex 1, resulting in reduced ATP levels and accumulation of AMP. Gluconeogenesis is reduced as a result of ATP deficit limiting glucose synthesis, increased AMP levels leading to reduced activity of the key gluconeogenic enzyme FBPase, inhibition of adenylate cyclase and cAMP-PKA signaling, and inhibition of mGPD contributing to altered redox state and reduced conversion of glycerol to glucose. Metformin-induced change in AMP/ATP ratio also activates AMPK, which suppresses lipid synthesis and exerts insulin sensitizing effects. Abbreviations: ACC, acetyl CoA carboxylase; AMPK, AMP-activated protein kinase; cAMP, cyclic AMP; complex 1, respiratory-chain complex 1; DHAP, dihydroxyacetone phosphate; FBPase, fructose-1,6-bisphosphatase; G3P, glycerol-3-phosphate; cGPD, cytosolic glycerophosphate dehydrogenase; mGPD, mitochondrial glycerophosphate dehydrogenase; OCT1, organic transporter 1; PKA, protein kinase A. Metformin is currently the first-line drug treatment for type 2 diabetes. Besides its glucose-lowering effect, there is interest in actions of the drug of potential relevance to cardiovascular diseases and cancer. However, the underlying mechanisms of action remain elusive. Convincing data place energy metabolism at the center of metformin’s mechanism of action in diabetes and may also be of importance in cardiovascular diseases and cancer. Metformin-induced activation of the energy-sensor AMPK is well documented, but may not account for all actions of the drug. Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action. Main Text Introduction Me Continue reading >>

Glucophage

Glucophage

GLUCOPHAGE® (metformin hydrochloride) Tablets GLUCOPHAGE® XR (metformin hydrochloride) Extended-Release Tablets DESCRIPTION GLUCOPHAGE® (metformin hydrochloride) Tablets and GLUCOPHAGE® XR (metformin hydrochloride) Extended-Release Tablets are oral antihyperglycemic drugs used in the management of type 2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. The structural formula is as shown: Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C4H11N5 HCl and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pK of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. GLUCOPHAGE tablets contain 500 mg, 850 mg, or 1000 mg of metformin hydrochloride. Each tablet contains the inactive ingredients povidone and magnesium stearate. In addition, the coating for the 500 mg and 850 mg tablets contains hypromellose and the coating for the 1000 mg tablet contains hypromellose and polyethylene glycol. GLUCOPHAGE XR contains 500 mg or 750 mg of metformin hydrochloride as the active ingredient. GLUCOPHAGE XR 500 mg tablets contain the inactive ingredients sodium carboxymethyl cellulose, hypromellose, microcrystalline cellulose, and magnesium stearate. GLUCOPHAGE XR 750 mg tablets contain the inactive ingredients sodium carboxymethyl cellulose, hypromellose, and magnesium stearate. System Components And Performance GLUCOPHAGE XR comprises a dual hydrophilic polymer matrix system. Metformin hydrochloride is combined with a drug release controlling polymer to form an “inne Continue reading >>

Cellular Effects Of Metformin, A Drug For Diabetes Mellitus

Cellular Effects Of Metformin, A Drug For Diabetes Mellitus

Type II diabetes mellitus is caused by a relative lack of or resistance to the protein insulin, which functions in maintaining normal blood sugar levels by facilitating transport of glucose into cells. Metformin is a common, effective medication for Type II diabetes mellitus. The drug has been shown to reduce rates of gluconeogenesis and increase uptake of glucose from the blood by skeletal muscles, but its specific mechanism of action is unknown. Researchers investigating metformin’s mechanism of action isolated hepatocytes from rats. They suspected metformin may interact with AMPK, a protein involved with a wide range of metabolic effects, such as increasing hepatic fatty acid oxidation, reducing hepatic glucose production (HGP), and reducing insulin secretion by beta cells of the pancreas. The researchers examined the activity of AMPK in hepatocytes treated with metformin, AMP (an endogenous allosteric activator of AMPK), or a control solution. The cells treated with metformin were found to have increased AMPK activity compared to the control solution (Figure 1a). The researchers performed a similar experiment in vitro with purified AMPK and its downstream substrate and found that metformin had no effect on AMPK activity (Figure 1b). Figure 1: The effect of metformin on AMPK activity was measured in hepatocytes (a) and in vitro (b). Hepatocytes were incubated for one hour with a buffered solution (negative control), AMP (positive control), or a specified concentration of metformin. White: control solution; gray: AMP; black: metformin. *P < 0.05, **P < 0.01 The researchers also discovered an inhibitor called Compound K that directly interacts with AMPK. Adding the inhibitor to hepatocytes incubated with metformin showed that Compound K attenuates metformin’s abili Continue reading >>

Metformin For Treatment Of The Polycystic Ovary Syndrome

Metformin For Treatment Of The Polycystic Ovary Syndrome

INTRODUCTION The polycystic ovary syndrome (PCOS) is characterized by both oligo/amenorrhea and androgen excess in women. When fully expressed, the manifestations include irregular menstrual cycles, hirsutism, obesity, and a constellation of cardiometabolic disturbances. It is a common endocrinopathy, occurring in 5 to 7 percent of reproductive age women [1-3]. The use of metformin in the management of PCOS will be reviewed here. The clinical manifestations, diagnosis, and other treatment options for PCOS are reviewed separately. (See "Clinical manifestations of polycystic ovary syndrome in adults" and "Diagnosis of polycystic ovary syndrome in adults" and "Treatment of polycystic ovary syndrome in adults".) OVERVIEW Interest in the use of metformin, an insulin-lowering drug, in PCOS increased when it was appreciated that insulin resistance played an important role in the pathophysiology of the disorder. Metformin is typically the first-line treatment for patients with type 2 diabetes; it is not approved for use in prediabetes or PCOS, although it is often prescribed for treatment of these conditions. Early trials in women with PCOS subsequently demonstrated a small benefit for weight reduction, a decrease in serum androgens (without improvement in hirsutism), and restoration of menstrual cycles in approximately 50 percent of women with oligomenorrhea (although not always ovulatory). Early data also suggested that metformin was effective for ovulation induction in anovulatory women with PCOS. As a result, metformin was used "off-label" for a number of these indications [4,5]. Although there was widespread enthusiasm for metformin therapy in women with PCOS for a number of years, clinical data do not support the use of metformin for treatment of hirsutism or as first-lin Continue reading >>

Metformin (glucophage) And Weight Loss

Metformin (glucophage) And Weight Loss

Tweet Metformin, a generic diabetes treatment usually sold under the brand name Glucophage, may help people with diabetes to lose weight by lowering their appetites. Insulin makes people overweight by acting on the brain to cause hunger, making the liver manufacture fat and fill fat cells in the stomach. Avoiding obesity is a matter of avoiding foods high in blood sugar, and taking medication that prevents blood sugar levels from climbing too high. Glucophage function The function of diabetes drug Glucophage is to reduce the release levels of sugar from your liver. This stops blood glucose levels from rising too high, and means that the body does not have to produce as much insulin. Therefore, the patient is not as hungry. Type 2 diabetes drug Metformin (Glucophage) may be used successfully as a medication for type 2 diabetes. Lowers insulin levels It lowers insulin levels, helps to prevent diabetes complications, and helps people with diabetes to lose weight. Losing weight whilst taking Metformin (Glucophage) means also eating a healthy diet. Eating lots of foods that boost blood sugar levels will counteract the effects of Metformin. Most doctors prescribe 500mg of Metformin (Glucophage) before eating. Tweet Type 2 diabetes mellitus is a metabolic disorder that results in hyperglycemia (high blood glucose levels) due to the body: Being ineffective at using the insulin it has produced; also known as insulin resistance and/or Being unable to produce enough insulin Type 2 diabetes is characterised by the body being unable to metabolise glucose (a simple sugar). This leads to high levels of blood glucose which over time may damage the organs of the body. From this, it can be understood that for someone with diabetes something that is food for ordinary people can become a s Continue reading >>

Metformin And Sitagliptin (janumet)

Metformin And Sitagliptin (janumet)

are allergic to dapagliflozin or any of the ingredients in FARXIGA. Symptoms of a serious allergic reaction may include skin rash, raised red patches on your skin (hives), swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing. If you have any of these symptoms, stop taking FARXIGA and contact your healthcare provider or go to the nearest hospital emergency room right away have severe kidney problems or are on dialysis. Your healthcare provider should do blood tests to check how well your kidneys are working before and during your treatment with FARXIGA Dehydration (the loss of body water and salt), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at a higher risk of dehydration if you have low blood pressure; take medicines to lower your blood pressure, including water pills (diuretics); are 65 years of age or older; are on a low salt diet, or have kidney problems Ketoacidosis occurred in people with type 1 and type 2 diabetes during treatment with FARXIGA. Ketoacidosis is a serious condition which may require hospitalization and may lead to death. Symptoms may include nausea, tiredness, vomiting, trouble breathing, and abdominal pain. If you get any of these symptoms, stop taking FARXIGA and call your healthcare provider right away. If possible, check for ketones in your urine or blood, even if your blood sugar is less than 250 mg/dL Kidney problems. Sudden kidney injury occurred in people taking FARXIGA. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or excessive heat exposure Serious urinary tract infections (UTI), some that lead to hospitalization, occu Continue reading >>

Review Metformin: From Mechanisms Of Action To Therapies

Review Metformin: From Mechanisms Of Action To Therapies

Metformin is currently the first-line drug treatment for type 2 diabetes. Besides its glucose-lowering effect, there is interest in actions of the drug of potential relevance to cardiovascular diseases and cancer. However, the underlying mechanisms of action remain elusive. Convincing data place energy metabolism at the center of metformin’s mechanism of action in diabetes and may also be of importance in cardiovascular diseases and cancer. Metformin-induced activation of the energy-sensor AMPK is well documented, but may not account for all actions of the drug. Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action. Continue reading >>

Metformin: Indication, Dosage, Side Effect, Precaution | Mims.com Malaysia

Metformin: Indication, Dosage, Side Effect, Precaution | Mims.com Malaysia

Adult : PO Conventional preparation: Initial: 500 mg bid or tid, or 850 mg 1-2 times daily, may increase gradually to 2000-3000 mg/day at intervals of at least 1 wk. Modified-release preparation: Initial: 500 mg once daily, may increase in increments of 500 mg at intervals of at least 1 wk to max 2000 mg once daily at night. If glycaemic control is not sufficient, dose may be divided to give 1000 mg bid. Doses >2000 mg/day, admin the conventional preparation. Adult: Conventional preparation: Initially, 500 mg bid or tid, or 850 mg 1-2 times daily, may increase gradually to 2000-3000 mg daily at intervals of at least 1 wk. Modified-release preparation: Initially, 500 mg once daily, may increase in increments of 500 mg at intervals of at least 1 wk to max 2000 mg once daily at night. If glycaemic control is not sufficient, dose may be divided to give 1000 mg bid. Doses >2000 mg daily, admin the conventional preparation. Child: 10 yr Initially, 500 mg 1-2 times daily or 850 mg once daily, may increase gradually to max 2000 mg daily in 2 or 3 divided doses at intervals of at least 1 wk. Elderly: Initial and maintenance dosing should be conservative. Patient w/ acute or chronic metabolic acidosis, including diabetic ketoacidosis w/ or w/o coma; undergoing surgery. Intravascular admin of iodinated contrast agents. Renal impairment (CrCl <60 mL/min). Patient w/ CHF requiring drug therapy, cardiac or resp failure, recent MI, shock. Patient exposed to stress-related states (e.g. fever, trauma, infection, surgery). Hepatic impairment. Elderly. Pregnancy and lactation. Anorexia, nausea, vomiting, diarrhoea, abdominal pain, taste disturbance, hepatitis. Rarely, decreased vit B12 absorption, erythema, pruritus and urticaria. Category B: Either animal-reproduction studies have not d 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 >>

Metforminmode Of Action And Clinical Implications For Diabetes And Cancer

Metforminmode Of Action And Clinical Implications For Diabetes And Cancer

Metforminmode of action and clinical implications for diabetes and cancer Mrta Korbonits, MD, PhD is Professor of Endocrinology and Metabolism at Queen Mary University of London. Her primary research interests are the hormonal regulation of AMPK, pituitary diseases and familial pituitary adenomas. Nature Reviews Endocrinology volume 10, pages 143156 (2014) Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the mechanistic aspects of metformin action remained ill-defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signalling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us to develop novel treatments. The centre of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation. Here, we discuss the updated understanding of the antigluconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mell 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 - Mechanism Of Action

Metformin - Mechanism Of Action

Decreases intestinal absorption of glucose improves insulin sensitivity by increasing peripheral glucose uptake and utilization Metformin improve glucose utilization in skeletal muscle and adipose tissue by increasing cell membrane glucose transport. This effect may be due to improved binding of insulin to insulin receptors since metformin is not effective in diabetics without some residual functioning pancreatic islet cells rarely causes hypoglycemia since it does not significantly change insulin concentrations -----------------------------------------Information from Clinical Pharmacology-------------------------- Mechanism of Action: Metformin is an antihyperglycemic agent that improves glucose tolerance, lowering both basal and postprandial plasma glucose with mechanisms different from other classes of oral antidiabetic agents. Metformin decreases hepatic gluconeogenesis production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease. Metformin improve glucose utilization in skeletal muscle and adipose tissue by increasing cell membrane glucose transport. This effect may be due to improved binding of insulin to insulin receptors since metformin is not effective in diabetics without some residual functioning pancreatic islet cells. [24568 ] Unlike the sulfonylureas, metformin rarely causes hypoglycemia since it does not significantly change insulin concentrations. An important distinction is that sulfonylureas increase insulin secretion thus making them useful in non-obese patients with type 2 diabetes while metformin improves insulin resis Continue reading >>

Understanding The Benefit Of Metformin Use In Cancer Treatment

Understanding The Benefit Of Metformin Use In Cancer Treatment

Understanding the benefit of metformin use in cancer treatment Dowling et al; licensee BioMed Central Ltd.2011 Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed. MetforminmTOR SignalingPhenforminMetformin ActionPotential Anticancer Effect The biguanides metformin, phenformin and buformin are derived from the herb Galega officinalis (French lilac, also known as Goat's Rue or Italian Fitch) and were originally developed for the treatment of hyperglycemia and type 2 diabetes. Use of tea infused with French lilac for relief of frequent urination (polyuria) and halitosis (a sweet odor on breath), both now well known symptoms of diabetes, dates back to ancient Egypt and medieval Europe [ 1 3 ]. Work in the 1920 s identified biguanides as the active compounds from the French lilac and led to their development as therapeutics in the 1950 s [ 1 , 3 , 4 ]. While phenformin and buformin were withdrawn from the market in the 1970 s due to toxicity related to lactic acidosis, metformin (N',N'-dimethylbiguanide) remains one of the most commonly prescribed drugs, with 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 >>

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