Antidiabetic Drugs

Posts Tagged ‘Glucophage’

Commonly, women with type 2 diabetes are taking sulphonylureas and/or metformin prior to conception. Hitherto, these have little place in the management of diabetes in pregnancy, although the use of metformin has been attracting increasing interest in recent years. The main anxiety about sulphonylureas in pregnancy is the possibility of further increasing the degree of fetal hyperinsulinaemia by direct drug-induced stimulation. Sulphonylureas, with the exception of glyburide, cross the placenta and have been implicated as a direct cause of neonatal hypoglycaemia. The long-acting agent chlorpropamide is particularly dangerous and should not be used in the last 4 weeks of gestation. There is no convincing evidence that these drugs are teratogenic. Metformin, which does not cross the placenta, has been reported to be useful in some obese individuals with type 2 diabetics who are inadequately controlled by diet. There are a range of theoretical and practical benefits from using metformin therapy instead of insulin therapy in later pregnancy, but there is insufficient data currently to support its routine usage. Several reports of the use of metformin during pregnancy in women with polycystic ovary syndrome have not shown adverse pregnancy outcomes. In these women, taking metformin before, during the first trimester or throughout pregnancy reduced rates of spontaneous abortion and normal growth development, and normal maternal morbidity and mortality rates are observed. There is also a reduced subsequent risk of gestational diabetes with continued use of metformin during pregnancy. Most authorities, however, continue to recommend that metformin is not routinely used except where any potential harm is outweighed by the benefits of metformin usage, e.g., severe insulin resistance or refusal to use insulin. Glitazones are unlicensed for use in pregnancy and are not recommended.

Drug Approvals

(British Approved Name Modified, US Adopted Name, rINN)

International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish):

Hidrocloruro de metformina; LA-6023 (metformin or metformin hydrochloride); Metformiinihydrokloridi; Metformin Hidroklorur; Metformin hydrochlorid; Metformine, chlorhydrate de; Metformin-hidroklorid; Metforminhydroklorid; Metformini hydrochloridum; Metformino hidrochloridas.

C₄H₁₁N₅,HCI = 165,6.

CAS — 657-24-9 (metformin); 1115-70-4 (metformin hydrochloride).

ATC — A10BA02.

Pharmacopoeias. In China, Europe, Japan, and US.

European Pharmacopoeia, 6th ed. (Metformin Hydrochlonde). White or almost white crystals. Freely soluble in water slightly soluble in alcohol practically insoluble in acetone and in dichloromethane.

The United States Pharmacopeia 31, 2008 (Metformin Hydrochloride). A white crystalline powder. Freely soluble in water slightly soluble in alcohol practically insoluble in acetone and in dichloromethane.

Adverse Effects, Treatment, and Precautions

As for biguanides in general.

Breast feeding. Based on animal studies the UK and US licensed product information warns that metformin may be distributed into breast milk, and that the possible effects on the infant should be considered if women wish to breast feed while receiving the drug. However, a study in 7 breast-feeding women receiving metformin at a median dose of 1.5 g daily found the concentrations in milk to be about a third of those in maternal plasma, resulting in a mean calculated dose to the infants of 40 micrograms/kg daily. Blood samples were taken from 4 of the infants: metformin concentrations were undetectable in 2, and were very low (10 to 15% of maternal values) in the others. Given these results the authors considered that women receiving metformin need not be discouraged from breast feeding. Similar results from 3 other studies’ that included 13 women have provided further evidence that metformin is distributed into breast milk, that concentrations in milk are less than those in maternal plasma, and that breast-fed infants would be exposed to a very small percentage of the maternal dose. Six infants were breastfed with no adverse effects that could be attributed to metformin. A prospective study of weight, height, and motor-social development over 6 months, in infants of women taking metformin (1.5 to 2.55 g daily) for poly cystic ovary syndrome, found no difference between 61 infants who were breast-fed and 50 who were formula-fed.

Fasting. For the view that metformin could be used with little risk of hypoglycaemia in fasting Muslim patients during Ramadan, and suggestions for modifying the timing of doses, see under Precautions of Insulin.

Pregnancy. Insulin is generally preferred for treatment of diabetes during pregnancy. However, there are limited data to suggest that metformin does not increase the risk of congenital abnormalities and does not adversely affect pregnancy outcome in diabetic women. A controlled study comparing insulin with metformin in gestational diabetes is underway.The use of metformin to improve ovulation in polycystic ovary syndrome (PCOS) is increasing. There is growing evidence to suggest that metformin used before and during pregnancy in these women does not increase the risk of congenital abnormalities, and may reduce first trimester spontaneous abortion,’which is common in women with PCOS.

Interactions

As for biguanides in general.

Pharmacokinetics

Metformin hydrochloride is slowly and incompletely absorbed from the gastrointestinal tract the absolute bioavailability of a single 500-mg dose is reported to be about 50 to 60%, although this is reduced somewhat if taken with food. Once absorbed, protein binding in plasma is negligible the drug is excreted unchanged in the urine. The plasma elimination half-life is reported to range from about 2 to 6 hours after oral doses. Metformin crosses the placenta and is distributed into breast milk in small amounts.

Uses and Administration

Metformin hydrochloride is a biguanide antidiabetic. It is given orally in the treatment of type 2 diabetes mellitus, and is the drug of first choice in overweight patients. Initial dosage is 500 mg two or three times daily or 850 mg once or twice daily with or after meals, gradually increased if necessary, at intervals of at least 1 week, to 2 to 3 g daily doses of 3 g daily are associated with an increased incidence of gastrointestinal adverse effects. Gastrointestinal effects are also common on beginning therapy, and the BNF recommends starting therapy more gradually with 500 mg at breakfast for at least 1 week, then increasing to 500 mg twice daily for at least 1 week, with further increases as required, up to a usual maximum of 2 g daily in 3 divided doses with meals. A modified-re-lease preparation is also available, which is given in an initial dose of 500 mg once daily and may be increased in increments of 500 mg, at intervals of at least 1 week, to a maximum of 2 g once daily with the evening meal. If glycaemic control is not adequate the dose may be divided to give 1 g twice daily with meals. If doses above 2 g daily are required, they should be given as the standard preparation. For doses used in children and adolescents, see below.

Metformin is also used as the chlorophenoxyacetate and as the embonate.

Action. A review of the action of metformin considered that although a number of possible mechanisms have been suggested, the major action of metformin lay in increasing glucose transport across the cell membrane in skeletal muscle. There is also some evidence in vitro that it can inhibit the formation of advanced glycosylation end-products.

Administration in children. In children aged 10 years and older with type 2 diabetes mellitus, oral metformin hydrochloride may be used in a starting dose of 500 mg or 850 mg once daily, or 500 mg twice daily, given with or after a meal. It may be gradually increased if needed, at intervals of at least 1 week, to a maximum of 2 g daily given in 2 or 3 divided doses. Modified-release preparations are generally not licensed for use in children.

Although rare, the incidence of type 2 diabetes is increasing in children and adolescents, related in part to the increase in obesity occurring particularly in westernised countries. A small placebo-controlled study of patients aged 10 to 17 years with type 2 diabetes found that metformin improved glycaemic control and that adverse effects were similar to those in adults. In obese children and adolescents with hyperinsulinaemia, who are at risk of developing type 2 diabetes, small studies of metformin use have reported improvements in body composition and fasting insulin concentrations. There has also been some interest in the use of metformin as an adjunct to insulin in adolescents with type 1 diabetes improvements in glycaemic control and reductions in insulin doses have been reported.

Diabetes mellitus. Results of the United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive blood glucose control with metformin reduces the risk of diabetic complications and death in overweight patients with type 2 diabetes.The study also generated some concern regarding intensive therapy with metformin plus a sulfonylurea (see under Interactions) but this was not borne out on further analysis and such combinations are widely used. Metformin is also used with the thiazolidinediones, or with insulin in patients requiring combined or more intensive therapy. Metformin has also been investigated for the prevention of type 2 diabetes in patients at high risk. Although metformin treatment for an average 2.8 years reduced the incidence of type 2 diabetes by 31% in a study of patients with impaired glucose tolerance, intensive lifestyle modification was actually more effective (58% reduction). Lifestyle modification was also more effective than metformin in reducing cardiovascular risk factors and the development of the metabolic syndrome. The durability of these effects is unknown but follow-up of this study is ongoing.

There is some interest in using oral hypoglycaemics as adjuncts to insulin therapy in patients with type 1 diabetes. Short-term results from small studies have suggested that metformin may be beneficial, in this context, in adolescents with pubertal insulin resistance (see also Administration in Children, above) and perhaps in adults who are overweight or otherwise at risk of reduced insulin sensitivity.

Polycystic ovary syndrome. It has been suggested that hyper -insulinism may play a pathogenetic role in stimulating the abnormal androgen production from the ovary seen in women with polycystic ovary syndrome (PCOS). Most early studies ofmetformin in PCOS were small, observational, and of short duration, with mixed results. Although there were reports of reduced insulin levels, increased insulin sensitivity, and improved androgen concentrations, other studies failed to confirm these effects. Later randomised studies were also small, but some were of longer duration. These reported weight reductions of obese patients, reductions in insulin levels and increased sensitivity, improved androgen and other hormonal measures, improved menstrual patterns, and reduced hirsutism, but again, not consistently. Metformin has also been reported to increase the rate of spontaneous ovulation, and may improve the outcome of IVF procedures. Combination ofmetformin with clo-mifene appeared to improve ovulatory response, compared with clomifene alone, in studies of women with PCOS, though there is also a report of no apparent benefit. Furthermore, 2 large, placebo-controlled studies have found that metformin, either alone or with clomifene, did not improve the rate of ovulation, pregnancy, or live births in women with polycystic ovary syndrome.

Some consider that current evidence supports a trial ofmetformin in patients with anovulation, androgen excess, and vascular risk factors, but because of the lack of data on long-term safety such use should be supervised by an endocrinologist or a physician with suitable expertise.

Preparations

British Pharmacopoeia 2008: Metformin Tablets

The United States Pharmacopeia 31, 2008: Glipizide and Metformin Hydrochloride Tablets; Glyburide and Metformin Hydrochloride Tablets; Metformin Hydrochloride Extended-Release Tablets; Metformin Hydrochloride Tablets.

Proprietary Preparations

Argentina: Baligluc DBI AP Diab Dos Glucaminol Glucogood Glucophage Islotin Mectin Medobis Metforal Metfori † Oxemet Redugluc

Australia: Diabex Diaformin Glucohexal Glucomet Glucophage Novomet

Austria: Clonarol Desugar Diabetex Glucomin Glucophage Meglucon Orabet †

Belgium: Glucophage Metformax

Brazil: Diaformin Dimefor Formetf Formyn Glicefor Glifage Glucoformin Metfordin † Metformed Teutoformin

Canada: Glucophage Glumetza Glycon †

Chile: Diaglitab Fintaxim Glafornil Glicenex Glidanil Glifortex Glucophage Hipoglucin Menarini-Metforal †

Czech Republic: Adimet Diaphage Glucomerck Glucophage Gluformin Glumetsan Langerin Metfirex Metfogamma Siofor Stadamet

Denmark: Glucophage Orabet

Finland: Diformin Glucophage Metforem Oramet

France: Diabamyl † Glucophage Stagid

Germany: Biocos Diabesin Diabetase † Espaformin † Glucobon Glucophage Juformin Mediabet Meglucon Mescorit Met Metfodoc Metfogamma Metfor † Metform † MetSurrir Siofor Thiabet

Greece: Glucofree Glucophage Metforil Sukontrol

Hong Kong: CP-Metform Diabetmin Diaformin Glucomet Glucophage Glumet Guamet Melbin

Hungary: Adimet Gluformin Maformin † Meforal Meglucon Merckformin Metfogamma Metrivin † Stadamet

India: Bigomet † Emfor Emnorm Exermet Formin † Glumet Glyciphage Glyree M Insumet Metlong Walaphage X-Met

Indonesia: Benofomin Diabex Eraphage Forbetes Formell Gliformin Glucofor Glucophage Glucotika Gludepatic Glufor Glumin Gradiab Methormyl Methpica Metphar Regius Tudiab Zumamet

Ireland: Glucophage

Israel: Apophage Glucomin Glucophage Glufor

Italy: Glucophage Metbay Metfonorm Metforal Metiguanide

Japan: Glycoran Melbin

Malaysia: Diabemet † Diabetmin Glucomet Glucophage Glumet Riomet Xmet

Mexico: Aglumet Anglucid Apozemia Dabex Debeone Dimefor Dinamel Ficonax Forlucyl Glucophage Glunovag Harbamind Ifor Meglubet Melbexa Mifelar Pharmafet Pre-Dial

The Netherlands: Diabex Dianorm † Finormet † Glucophage Glumeff Niformina

Norway: Glucophage

New Zealand: Glucomet Glucophage † Metomin

Philippines: Diafat Diazen Euform Fornidd Glucare Glucoform Glucomed Glucophage Glumet Glyformin Horsulin Humamet L-Max Insunex Neoform Nidcor Sucranorm Vimetrol Xmet

Poland: Glucophage † Gluformin Metfogamma Metformax Metifor Siofor

Portugal: Diabex Glucophage Mekoll Risidon Stagid

Russia: Bagomet Formin Gliformin Glucophage Metfogamma Siofor

South Africa: Glucophage Metforal

Singapore: Diabetmin Diamin † Glucophage Glycomet Glycoran † Metforal

Spain: Dianben

Sweden: Glucophage

Switzerland: Gluconormine Glucophage Metfin

Thailand: Ammiformin Deson Diamet Formin Gluco Glucoles-500 Glucolyte Glucomet † Glucono Glucophage Gluformin Glustress † Glutabloc Gluzolyte Macromin † Maformin ME-F † Meformed Metfor Metfron Miformin Pocophage Poli-Formin Prophage Serformin Siamformet

Turkey: Glifor Glucophage Gluformin Glukofen

UAE: Dialon

UK: Glucophage Metsol

USA: Fortamet Glucophage Glumetza Riomet

Venezuela: Diaformina DimeforF Glafornil Glucaminol Glucofage

Multi-ingredient

Argentina: Avandamet DBI Duo Glucovance Gludex Plus Isloglib Medobis G Metformin Duo Rosiglit-Met

Australia: Avandamet Glucovance

Belgium: Avandamet Glucovance

Brazil: Glucovance Starform

Canada: Avandamet

Chile: Avandamet Bi-Euglucon M Diaglitab Plus Glifortex-G Glimet Glucovance Glukaut Hipoglucin DA

Czech Republic: Avandamet Competact Eucreas Glibomet Glubrava Glucovance

Denmark: Avandamet

Finland: Avandamet

France: Avandamet Competact Eucreas Glucovance

Germany: Avandamet

Greece: Avandamet Normell

Hong Kong: Avandamet Glucovance

Hungary: Avandamet

India: Betaglim M † Diaforte Diaglip M Exermet GM Exermet GZ Exermet P Gliclamet Glimiprex MF Glimulin-MF † Glinil M Glizid-M Glycigon-M Glycinorm M Glygard M Metaglez P-Glitz M Piomed M Piosafe MF Roglin-M Rosicon MF

Indonesia: Avandamet Glucovance

Ireland: Avandamet

Israel: Avandamet

Italy: Avandamet Bi-Euglucon M Glibomet Gliconorm Glicorest Glucomide Pleiamide Suguan M

Malaysia: Avandamet Glucovance

Mexico: Apometglu Avandamet Bi-Dizalon Bi-Euglucon M Bi-Pradia Duo-Anglucid Glimetal Glucotec Glucovance Imalet Insogen Plus Insusym-Forte Maviglin Mellitron Midaphar-ma Mifelar-C Nadib-M Norfaben M Obinese Sibet-C Sil-Norboral Wadil

The Netherlands: Avandamet Glucovance

Norway: Avandamet

Philippines: Avandamet Euglo Plus Glucovance

Poland: Avandamet

Portugal: Avandamet Competact Glucovance

Russia: Glibomet Glucovance

South Africa: Glucovance

Singapore: Avandamet Glucovance

Spain: Avandamet

Sweden: Avandamet

Switzerland: Avandamet Diabiformine Glucovance

Thailand: Avandamet

UK* Avandamet Competact Eucreas

USA: Actoplus Met Avandamet Diofen Glucovance Glybofen Janumet Metaglip

Venezuela: Avandamet Bi-Euglucon Diaformina Plus Glucovance Starform

The symbol † denotes a preparation no longer actively marketed.

Approximately 40% of all type 2 diabetics take a drug from the sulfonylurea class (see TABLE 2) — usually glyburide, glipizide, or chlorpropamide. The sulfonylureas cause the beta-cells of the pancreas to increase insulin secretion. Weight gain is common with sulfonylurea use and ranges from 1.8 to 2.8 kg.

Table 2. Antidiabetic Drugs Used to Treat Type 2 Diabetes
Drug	Mechanism of Action	Effect on Weight During Initiation of Therapy up to One Year	Potential Side Effects
Sulfonylureas	Increased insulin secretion by pancreatic beta cells	1.8 to 2.8 kg weight gain	Weight gain, hypoglycemia
Metformin	Decreased hepatic glucose production/enhanced glucosedisposal by skeletal muscle	0.6 to 0.8 kg weight reduction	Abdominal bloating, nausea, cramping,  diarrhea
Acarbose	Inhibits alpha-glucosidase and alpha-amylase	None or negligible	Flatulence, diarrhea, abdominal discomfort
Troglitazone	Increased glucose disposal in muscle tissue/decreased hepatic glucose production	None to 0.6 kg weight gain	Few reported (jaundice due to idiosyncratic drug reaction)
Insulin	Normal physiologic effects	Up to 6.0 kg weight gain	Hypoglycemia

Metformin (Glucophage) is a biguanide antidiabetic agent that reduces basal hepatic glucose production by altering gluconeogenesis and/or glycogenolysis. Additionally, metformin decreases insulin resistance by promoting insulin-sensitive glucose uptake by muscle cells. Metformin can also reduce triglycerides and low-density lipoprotein (LDL) cholesterol, and increase high-density lipoprotein (HDL) cholesterol. Weight reductions of 0.6 to 0.8 kg have been noted in study subjects taking metformin.When metformin is combined with the sulfonylurea glyburide, however, average weight gains of 0.7 kg have been reported.

Acarbose (Precose) is an alpha-glucosidase inhibitor as well as an inhibitor of pancreatic alpha-amylase. These enzymes are responsible for the hydrolysis of oligosaccharides and related saccharides in the small intestine. Inhibition of these enzymes results in reductions in the rate and extent of carbohydrate digestion and absorption of glucose in the body. Patients treated with acarbose tend to experience no changes in weight or serum lipids.

Troglitazone (Rezulin) belongs to a new class of drugs called thiazolidinediones. It works by decreasing insulin resistance. Its primary actions involve increasing glucose disposal from the blood stream into muscle tissue and decreasing glucose production in the liver. No or very small weight changes in patients taking troglitazone are seen. Decreases in plasma triglyceride and free fatty acid levels have also been reported.

Approximately three-quarters of all the insulin used in the U.S. is taken by people with type 2 diabetes. Exogenous insulin reduces hepatic glucose production in type 2 diabetics. It also increases insulin-stimulated glucose utilization and endogenous insulin secretion. Weight gain is common in patients using insulin and may include gains up to 6.0 kg in a 12-month period.

Patient-Specific Considerations

New antidiabetic agents were approved for the U.S. market. They are metformin, acarbose and glimepiride. Precautions associated with their use in the patient with renal insufficiency will now be described.

Metformin (Glucophage): The biguanide hypoglycemic agent metformin (Glucophage) is approved for use in the treatment of diabetes mellitus. Metformin is indicated for use as an adjunct to diet and/or a sulfonylurea agent when either of these treatment regimens does not control hyperglycemia. The mechanism of action for metformin differs from the sulfonylureas. Metformin decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and use and by decreasing hepatic glucose production. The primary concern with metformin is the development of lactic acidosis, especially in patients with renal insufficiency.

Metformin is a congener of phenformin, also a biguanide hypoglycemic agent, which was pulled off the market in the U.S. in 1977 due to concerns with phenformin causing lactic acidosis. Metformin has also been associated with causing lactic acidosis; however, the rate of metformin-associated lactic acidosis is one-tenth that of phenformin (one in 4,000 vs. one in 40,000 – 80,000). Cases of metformin-induced lactic acidosis have occurred primarily in patients with renal insufficiency and increased age.

The biguanides can induce lactic acidosis through an increase in cellular lactate production and a decrease in the hepatic metabolism of lactate. Diabetic patients are particularly at high risk for metformin-induced lactic acidosis due to their predisposition to renal dysfunction and impaired clearance of the drug, as well as their abnormal lactate metabolism. Due to the high risk of lactic acidosis in patients with renal dysfunction, metformin is contraindicated in patients with serum creatinine levels >1.5 mg/dL for males and >1.4 mg/dL for females.

The signs and symptoms of biguanide-induced lactic acidosis are nonspecific and include (in decreasing order of frequency) vomiting, somnolence, nausea, epigastric pain, anorexia, hyperpnea, lethargy, diarrhea and thirst. The hallmark of biguanide-associated lactic acidosis is severe lactic acidosis without evidence of hypoperfusion or hypoxia. The treatment of biguanide-induced lactic acidosis is support of the circulation and removal of the drug from the body.

Acarbose (Precose): Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. In patients with renal impairment, plasma concentrations of acarbose have been shown to be proportionally increased relative to the degree of renal dysfunction. Long-term clinical trials in diabetic patients with significant renal dysfunction (serum creatinine >2.0 mg/dL) have not been conducted. Therefore, treatment of these patients with acarbose is not recommended.

Glimepiride (Amaryl): Glimepiride is a new sulfonylurea blood glucose-lowering agent. Patients with renal impairment may be more sensitive to the glucose-lowering effect of glimepiride. Thus, in patients who have renal dysfunction, a starting dose of 1 mg once daily followed by appropriate dose titration is recommended. Pharmacist’s Involvement

With the provision of pharmaceutical care, the pharmacist should be closely involved with the diabetic patient in renal failure and can offer the patient assistance in several health-care areas, including the management of his/her diabetes. The pharmacist can educate the patient about diabetes, its complications and the importance of controlling blood glucose levels through proper diet, exercise and use of medications. The proper use of a blood glucose machine to monitor home blood glucose levels can also be taught by the pharmacist, as well as frequently measuring and monitoring the patient’s blood glucose. Since hypertension can worsen renal function, the pharmacist should also periodically monitor the patient’s blood pressure and teach the patient how to measure his or her blood pressure at home. In monitoring blood glucose and blood pressure, the pharmacist also needs to assess the patient’s diet, activity level and health status.

In addition, the pharmacist should evaluate the patient’s drug therapy — assessing not only the medication’s efficacy, but also the medication’s effect on blood glucose, blood pressure, electrolytes, lipids and renal function. The patient’s optimal drug therapy, lifestyle, blood glucose, blood pressure and renal function must be monitored to prevent further complications.Summary

Renal failure seriously impacts the quality of life and management of the diabetic patient. There are numerous patient considerations that the pharmacist must evaluate. Additionally, an understanding of the effect renal failure has on insulin greatly assists the pharmacist who is providing pharmaceutical care to the diabetic patient with renal insufficiency.

Why Switch From Glucophage?

Switching from Glucophage to Glucophage XR can help to make your daily routine less complicated and make it easier for you to stick with your medication. Plus, clinical studies have shown that the blood sugar lowering effect of Glucophage XR, taken once daily, is comparable to the original Glucophage.

Glucophage XR is an extended-release formulation of Glucophage; this means that unlike Glucophage, Glucophage XR is designed to be taken once daily. By switching from Glucophage to Glucophage XR, you may cut down on the number of times a day that you must take this type 2 diabetes medication.

If you are looking for an effective and convenient way to help lower your blood sugar levels, ask your doctor about switching to Glucophage XR today!

Ask Your Doctor

Why should you talk to your doctor or healthcare provider about new Glucophage XR?

* Glucophage XR is a once-daily dose of Glucophage® (metformin hydrochloride tablets). When diet and exercise are not enough, and medication is needed, Glucophage XR offers most type 2 diabetes patients convenient and effective blood sugar control.

* Glucophage XR’s extended-release formula is designed for convenient once-a-day dosing. This makes it easier to take your medication as prescribed, which helps to ensure that you achieve and maintain blood sugar control.

* Glucophage XR is from the makers of Glucophage, the number one prescribed diabetes pill.

Benefits

* Because Glucophage XR is an extended-release medication, it usually can be taken only once per day.

* In clinical trials, Glucophage XR was shown to be comparable to Glucophage in improving control of blood sugar levels.

* Glucophage XR offers the benefit of being a convenient and effective way to help lower blood sugar levels.

Taking control of type 2 diabetes includes regular exercise, weight control, and eating healthy foods. Another important step is taking your medication as prescribed. When it comes to medication, if you’re looking for effective and convenient blood sugar control, Glucophage XR may be the answer for you.

Taking Glucophage XR

* Follow your doctor’s instructions about how much medicine to take and when to take it. (Your doctor may slowly increase your dose until your blood sugar levels are better controlled.)

* You should take Glucophage XR with meals (typically the evening meal when dosed once-daily).

* Your doctor may prescribe other medication along with Glucophage XR to help you achieve the best control of your blood sugar levels. Follow your doctor’s instructions about any of these other medications.

* Continue your diet and exercise program and test your blood sugar regularly.

Your doctor will monitor your diabetes and may perform blood tests on you from time to time to make sure your kidneys and your liver are functioning normally. There is no evidence that Glucophage XR causes harm to the liver or kidneys, but it is important to make sure that they are working properly.

All people with type 2 diabetes have to work to keep the amount of sugar in their blood as near to normal as possible. This is called “being in control.” Studies have shown that good glucose control may prevent or delay complications of type 2 diabetes such as heart disease, kidney disease, or blindness.

Controlling your blood sugar levels can be an ongoing challenge. Many different factors affect your blood sugar levels, including diet, activity, stress, and overall health. Knowing how much to eat, how much to exercise, and how much medication and/or insulin to take can be difficult. Keep in mind that your type 2 diabetes care team is available for support.

Making Blood Sugar Control More Manageable

When you have type 2 diabetes, it is easy to get caught up in the day-to-day actions that are required to manage your condition. Sometimes all of the “shoulds” and “should nots” can feel overwhelming. To make your daily efforts more manageable, it may be helpful to think about all your reasons for controlling your blood sugar. You may want to consider posting a list of these reasons where you will see it often.

There are other approaches you can take that might make the steps along the way easier. Try Glucophage XR. For example, if you plan to increase your physical activity, start by taking a 15-minute walk 3 times a week. Then try walking longer or more often. Remember, a big part of the process is learning what works for you. Your healthcare team can help you construct a manageable diabetes care plan.

In addition to exercise, diet, and weight loss, some people with type 2 diabetes need medication to keep their blood sugar levels under control. If you require medication to help control your blood sugar, you may want to ask your doctor or healthcare professional if Glucophage XR may be right for you.

When a person is suspected of having type 2 diabetes, there are several different types of blood tests that may be used to diagnose the disease, including the fasting glucose test, the oral glucose tolerance test, and the random glucose test. Of these, the fasting glucose test is the preferred method because it is highly accurate and simple to perform.

This section provides information on commonly used tests to diagnose type 2 diabetes. Only your doctor or healthcare professional can determine if you have type 2 diabetes.

Fasting Glucose Test

Diabetes is most often diagnosed using a fasting glucose test. For this test, you will be asked to go without eating for 10 to 16 hours, usually overnight, before a blood sample is drawn. The test will measure the amount of glucose in your blood. If your glucose level is equal to or greater than 126 milligrams per deciliter (mg/dL) on two or more fasting glucose tests performed on different days, you have type 2 diabetes.

This chart shows how the fasting glucose test is interpreted.

If your fasting glucose level is:	This is what it means:
Less than 110 mg/dL	This is a normal fasting glucose level.
Less than 110 mg/dL, but you have symptoms of type 2 diabetes OR Between 110 mg/dL and 126 mg/dL	Although you do not have type 2 diabetes, these levels may indicate a condition known as impaired fasting glucose. Your healthcare professional may recommend another test to confirm this, usually an oral glucose tolerance test or a glycosylated hemoglobin test.
126 mg/dL or more	You may have type 2 diabetes. Your healthcare professional will repeat the test another day to confirm.

Oral Glucose Tolerance Test

In some instances, an oral glucose tolerance test may be performed to diagnose type 2 diabetes. When taking this test, you will usually be asked to eat a diet that is high in carbohydrates for 3 days. Before the test, you will have to fast for 10 to 16 hours, usually overnight. When you go to the office or laboratory, you will first have a fasting blood sample drawn. You will then be asked to drink a sweet liquid that contains glucose. Samples of your blood will be taken 5 times over a period of 3 hours. Your doctor or healthcare professional will give you specific instructions prior to having a glucose tolerance test.

In a person who does not have type 2 diabetes, the glucose (sugar) levels in the blood will rise and then fall quickly. In someone with type 2 diabetes, blood glucose levels will often rise higher than normal and will not drop as fast. If your blood sugar level is above 200 mg/dL at 2 hours, you may have diabetes. Your doctor or healthcare professional will either repeat the test or perform a fasting glucose test on a different day to confirm the diagnosis.

After an oral glucose tolerance test, if the blood glucose levels are somewhere between those of a person without type 2 diabetes and a person with type 2 diabetes, a person is said to have impaired glucose tolerance. Although people with this condition may not have type 2 diabetes, they are at increased risk of developing it. If you have impaired glucose tolerance, your doctor or healthcare professional may recommend that you lose weight and exercise to help manage your risk of developing type 2 diabetes.

This chart shows how the oral glucose tolerance test is interpreted.

If your glucose level is:	This is what it means:
Less than 140 mg/dL at 2 hours	This is normal.
Between 140 mg/dL and 200 mg/dL at the end of the test	You may have impaired glucose tolerance.
Greater than 200 mg/dL at 2 hours	You may have type 2 diabetes. Your healthcare professional will repeat the test on another day or perform a fasting to confirm.

Random Glucose Test

When symptoms of diabetes are present, a blood sample that is taken in a non-fasting state (otherwise known as a random blood sample) may be used to test for type 2 diabetes. In this case, a glucose (sugar) level of greater than 200 mg/dL accompanied by symptoms of hyperglycemia suggests a person may have type 2 diabetes. However, the result must be confirmed on another day by performing a fasting glucose test or an oral glucose tolerance test.

If you have been diagnosed with type 2 diabetes and diet and exercise no longer control your blood sugar, treatments are available that may help you lower your blood sugar levels. One such treatment is Glucophage XR. Ask your doctor or healthcare professional if Glucophage XR is right for you.

Type 2 diabetes often has no symptoms. If symptoms are present, they often develop gradually and go unnoticed until problems occur. In fact, many people have type 2 diabetes and don’t even know it. Early diagnosis and treatment for type 2 diabetes is important. See your doctor or healthcare professional immediately if you experience any of the following symptoms:

* Extreme thirst

* Frequent urination

* Extreme hunger

* Unexplained weight loss

* Unexplained fatigue

* Blurry vision

* Tingling or numbness in the hands, feet, or legs

* Itchy skin

* Frequent infections of the skin, gums, vagina, or bladder

* Slow healing of cuts and scrapes

If you learn that you have type 2 diabetes and diet and exercise are not enough, treatments are available that may help you control your blood sugar levels. One such treatment is Glucophage XR. Ask your doctor or healthcare professional if Glucophage XR may be right for you.

Although type 2 diabetes can occur in anyone, you are at greater risk for developing this disorder if you:

* Have a family member who has type 2 diabetes

* Are overweight

* Are over 65 years of age

* Are of African-American, Hispanic/Latino, American-Indian, Asian-American, or Pacific-Islander descent

* Have high blood pressure

* Have very high cholesterol or triglyceride levels

* Are not very physically active (get less than 30 minutes of exercise 3 days a week)

* Are a woman who developed type 2 diabetes while pregnant (a condition called gestational diabetes)

* Are a woman who has experienced an unexplained miscarriage or stillbirth or had babies weighing 9 pounds or more at birth

Take advantage of our interactive type 2 diabetes risk assessment tool.

If you are at risk for developing type 2 diabetes, there are several things you can do that may manage your risk, such as exercising regularly, eating healthy foods, and watching your weight. Your doctor or healthcare professional can work with you to develop a program that’s right for you.

If you have been diagnosed with type 2 diabetes and your doctor or healthcare professional has recommended that you control your blood sugar levels with medication in addition to eating healthy foods and exercising regularly, ask him or her if Glucophage XR is right for you.

Until the beginning of the 20th century, type 2 diabetes was fairly rare. It now affects more than 14 million Americans. Healthcare professionals believe that type 2 diabetes has become so common because increasing numbers of people are eating more, exercising less, and becoming overweight. In addition, people are living longer, so there are more people than ever before over the age of 40, and thus more people at risk for developing type 2 diabetes.

Some people may be more likely to develop type 2 diabetes because they have various risk factors, such as their genetic make-up, body type, and activity level.

People who carry a genetic trait for type 2 diabetes and who are overweight may develop type 2 diabetes more rapidly. In these people, extra body fat may cause cells to become resistant to the effects of insulin (called insulin resistance). When this happens, the pancreas attempts to compensate by producing more insulin. Eventually, the pancreas may not be able to keep up with the body’s demand for increased levels of insulin, causing an abnormal increase in blood sugar levels. This condition is called impaired glucose tolerance, which can potentially lead to type 2 diabetes, hypertension, and heart disease.

Fortunately, there are steps you can take that may help manage your risk of developing type 2 diabetes. Some people are able to avoid type 2 diabetes by making changes to their lifestyle, such as eating less and exercising more regularly. It is also important to look at other type 2 diabetes risk factors that you may have. Ask your doctor or healthcare professional how to manage your risk factors.

If you have been diagnosed with type 2 diabetes and diet and exercise cannot adequately control your blood sugar, effective medication is available. Glucophage XR is a convenient and effective way to help lower high blood sugar levels. See your doctor or healthcare professional to find out if treatment with Glucophage XR may be right for you.