Melatonin is a hormone found naturally in the body. Melatonin used as medicine is usually made synthetically in a laboratory. It is most commonly available in pill form, but melatonin is also available in forms that can be placed in the cheek or under the tongue. This allows the melatonin to be absorbed directly into the body. Some people take melatonin by mouth to adjust the body's internal clock. It is used for jet lag, for adjusting sleep-wake cycles in people whose daily work schedule changes (shift-work disorder), and for helping blind people establish a day and night cycle. Melatonin is also taken by mouth for the inability to fall asleep (insomnia); delayed sleep phase syndrome (DSPS); rapid eye movement sleep behavior disorder (RBD); insomnia associated with attention deficit-hyperactivity disorder (ADHD); insomnia associated with traumatic brain injury (TBI); and sleep problems in children with developmental disorders including autism, cerebral palsy, and intellectual disabilities. Komboglyze is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: • in patients inadequately controlled on their maximally tolerated dose of metformin alone • in combination with other medicinal products for the treatment of diabetes, including insulin, in patients inadequately controlled with metformin and these medicinal products (see sections 4.4, 4.5 and 5.1 for available data on different combinations). • in patients already being treated with the combination of saxagliptin and metformin as separate tablets. Patients not adequately controlled on metformin alone should receive a dose of this medicinal product equivalent to the total daily dose of saxagliptin 5 mg, dosed as 2.5 mg twice daily, plus the dose of metformin already being taken. For patients inadequately controlled on dual combination therapy of insulin and metformin, or for patients controlled on triple combination therapy of insulin, and metformin plus saxagliptin as separate tablets The dose of this medicinal product should provide saxagliptin 2.5 mg twice daily (5 mg total daily dose) and a dose of metformin similar to the dose already being taken. When this medicinal product is used in combination with insulin, a lower dose of insulin may be required to reduce the risk of hypoglycaemia (see section 4.4). For patients inadequately controlled on dual combination therapy of a sulphonylurea and metformin, or for patients switching from triple combination therapy of saxagliptin, metformin and a sulphonylurea taken as separate tablets The dose of this medicinal product should provide saxagliptin 2.5 mg twice daily (5 mg total daily dose), and a dose of metformin similar to the dose already being taken. When this medicinal product is used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be required to reduce the risk of hypoglycaemia (see section 4.4).
Not only has new research told us how metformin really works, but a new biomarker was found that can determine the optimal dose of metformin that should be used to get the best results for each patient. Research from the Johns Hopkins Children’s Center reveals that the drug most commonly used in Type 2 diabetics who don’t need insulin works on a much more basic level than once thought, treating persistently elevated blood sugar — the hallmark of Type 2 diabetes — by regulating the genes that control its production. Investigators say they have zeroed in on a specific segment of a protein called CBP made by the genetic switches involved in overproduction of glucose by the liver that could present new targets for drug therapy of the disease. In healthy people, the liver produces glucose during fasting to maintain normal levels of cell energy production. After people eat, the pancreas releases insulin, the hormone responsible for glucose absorption. Once insulin is released, the liver should turn down or turn off its glucose production, but in people with Type 2 diabetes, the liver fails to sense insulin and continues to make glucose. The condition, known as insulin resistance, is caused by a glitch in the communication between liver and pancreas. 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. Metastasis is an intricate process by which a small number of cancer cells from the primary tumor site undergo numerous alterations, which enables them to form secondary tumors at another and often multiple sites in the host. Transition of a cancer cell from epithelial to mesenchymal phenotype is thought to be the first step in the progression of metastasis. Recently, the recognition of cancer stem cells has added to the perplexity in understanding metastasis, as studies suggest cancer stem cells to be the originators of metastasis. All current and investigative drugs have been unable to prevent or reverse metastasis, as a result of which most metastatic cancers are incurable. A potential drug that can be considered is metformin, an oral hypoglycemic drug. In this review we discuss the potential of metformin in targeting both epithelial to mesenchymal transition and cancer stem cells in combating cancer metastases.
Apo-Metformin (CA), Co Metformin (CA), Dom-Metformin (CA), Fortamet, Gen-Metformin (CA), Glucophage, Glucophage XR, Glumetza, Glycon (CA), Med Metformin (CA), Metsol (UK), Novo-Metformin (CA), Nu-Metformin (CA), PHL-Metformin (CA), PMS-Metformin (CA), Ran-Metformin (CA), Ratio-Metformin (CA), Rhoxal-Metformin (CA), Riomet, Riva-Metformin (CA), Sandoz Metformin (CA) • Lactic acidosis is rare but serious (50% mortality) metabolic complication that can result from drug accumulation. Lactic acidosis is also linked to such conditions as diabetes mellitus and significant tissue hypoperfusion and hypoxemia. Lactic acidosis incidence in patients receiving drug is low; cases have occurred mainly in diabetics with significant renal insufficiency. Patients with unstable or acute heart failure at risk of hypoperfusion and hypoxemia are at increased lactic acidosis risk. • Lactic acidosis risk rises with age and degree of renal dysfunction, and may decrease significantly through regular renal monitoring and by using lowest effective dosage. Perform careful renal monitoring, especially in elderly patients. Withhold drug promptly if patient develops condition linked to hypoxemia, dehydration, or sepsis. Elderly patients are more likely to have decreased renal function; contraindicated in patients with renal impairment, carefully monitor renal function in the elderly and use with caution as age increases Not for use in patients 80 years unless normal renal function established Initial and maintenance dosing of metformin should be conservative in patients with advanced age due to the potential for decreased renal function in this population Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients Asthenia Diarrhea Flatulence Weakness Myalgia Upper respiratory tract infection Hypoglycemia GI complaints Lactic acidosis (rare) Low serum vitamin B-12 Nausea/vomiting Chest discomfort Chills Dizziness Abdominal distention Constipation Heartburn Dyspepsia 5 mmol/L), decreased blood p H, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio; when metformin is implicated as the cause of lactic acidosis, metformin plasma concentrations 5 mcg/m L are generally found Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment; if metformin-associated lactic acidosis is suspected, immediately discontinue Patients with CHF requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk for hypoperfusion and hypoxemia, are at an increased risk for lactic acidosis; the risk for lactic acidosis increases with the degree of renal dysfunction and the patient’s age Do not start in patients aged 80 years or older unless Cr Cl demonstrates that renal function is not reduced, because these patients are more susceptible to developing lactic acidosis; metformin should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis Should generally be avoided in patients with clinical or laboratory evidence of hepatic disease; patients should be cautioned against excessive alcohol intake, either acute or chronic, during metformin therapy because alcohol potentiates the effects of metformin on lactate metabolism Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an e GFR between 30-60 m L/minute/1.73 m²; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinate contrast The onset of lactic acidosis often is subtle and accompanied by nonspecific symptoms (eg, malaise, myalgias, respiratory distress, increasing somnolence, nonspecific abdominal distress); with marked acidosis, hypothermia, hypotension, and resistant bradyarrhythmias may occur; patients should be instructed regarding recognition of these symptoms and told to notify their physician immediately if the symptoms occur; metformin should be withdrawn until the situation is clarified; serum electrolytes, ketones, blood glucose, and, if indicated, blood p H, lactate levels, and even blood metformin levels may be useful Once a patient is stabilized on any dose level of metformin, GI symptoms, which are common during initiation of therapy, are unlikely to be drug related; later occurrences of GI symptoms could be due to lactic acidosis or other serious disease Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis who is lacking evidence of ketoacidosis (ketonuria and ketonemia); lactic acidosis is a medical emergency that must be treated in a hospital setting; in a patient with lactic acidosis who is taking metformin, the drug should be discontinued immediately and general supportive care measures promptly instituted; metformin is highly dialyzable (clearance up to 170 m L/min under good hemodynamic conditions); prompt hemodialysis is recommended to correct the acidosis and to remove the accumulated metformin; such management often results in prompt reversal of symptoms and recovery Increased risk of severe hypoglycemia especially in elderly, debilitated or malnourished, adrenal or pituitary insufficiency, dehydration, heavy alcohol use, hypoxic states, hepatic/renal impairment, stress due to infection, fever, trauma, or surgery Concomitant administration of insulin and insulin secretagogues (e.g., sulfonylurea) may increase risk of hypoglycemia; therefore, a lower dose of insulin or insulin secretagogue may be required to minimize risk of hypoglycemia when used in combination with metformin Withholding of food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension, and renal impairment; therapy should be temporarily discontinued while patients have restricted food and fluid intake Rare lactic acidosis may occur due to metformin accumulation; fatal in approximately 50% of cases; risk increases with age, degree of renal dysfunction, and with unstable or acute CHF; if metformin-associated lactic acidosis suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of therapy; in patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to170 m L/minute under good hemodynamic conditions); hemodialysis has often resulted in reversal of symptoms and recovery Possible increased risk of CV mortality May cause ovulation in anovulatory and premenopausal PCOS patients May be necessary to discontinue therapy with metformin and administer insulin if patient is exposed to stress (fever, trauma, infection), or experiences diabetic ketoacidosis Several of the postmarketing cases of metformin-associated lactic acidosis occurred in setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse (shock) acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; discontinue therapy when such events occur May impair vitamin B12 or calcium intake/absorption; monitor B12 serum concentrations periodically with long-term therapy Not indicated for use in patients with type 1 diabetes mellitus that are insulin dependent due to lack of efficacy Withhold in patients with dehydration and/or prerenal azotemia Conclusive evidence of macrovascular risk reduction with metformin not established Limited data with in pregnant women are not sufficient to determine drug-associated risk for major birth defects or miscarriage; published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk; poorly-controlled diabetes mellitus in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications; poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity Limited published studies report that metformin is present in human milk; however, there is insufficient information to determine effects of metformin on breastfed infant and no available information on effects of metformin on milk production; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from the underlying maternal condition The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.
Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. Class Effect on CV outcomes people with diabetes and CVD Likelihood of hypoglycemia Effect on weight Relative A1C lowering when added to metformin