Glucophage/Metformin

[Jana]

GENERIC NAME: metformin

BRAND NAME: Glucophage , Glucophage XR

DRUG CLASS AND MECHANISM: Metformin is an oral medication that lowers blood glucose (sugar) and is used for treating type 2 diabetes. Insulin is a hormone produced by the pancreas that lowers glucose levels in blood by reducing the amount of glucose made by the liver and by increasing the removal of glucose from the blood by muscle and fat tissues. Diabetes results because of reduced production of insulin and reduced uptake (and effects) of insulin on the body's tissues. Metformin acts by increasing the sensitivity of liver, muscle, fat, and other tissues to the uptake and effects of insulin. These actions lower the level of sugar in the blood. Unlike glucose-lowering drugs of the sulfonylurea class, e.g. glyburide (Micronase; Diabeta) or glipizide (Glucotrol), metformin does not increase the concentration of insulin in the blood and, therefore, does not cause excessively low blood glucose levels (hypoglycemia) when used alone. In scientific studies, metformin reduced the complications of diabetes such as heart disease, blindness and kidney disease. Metformin was approved by the FDA in December of 1994.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Metformin tablets: 500, 850, and 1000 mg. Glucophage XR (extended release) tablets: 500 and 750 mg

STORAGE: Store at room temperature between 20-25°C (68-77°F).

PRESCRIBED FOR: Metformin is used for treating type II diabetes in adults and children. It may be used alone or in combination with other diabetic medications. Metformin also has been used to prevent the development of diabetes in people at risk for diabetes and to treat polycystic ovaries.

DOSING: For adults, metformin usually is begun at a dose of 500 mg twice a day or 850 mg once daily. The dose is gradually increased by 500 mg weekly or 850 mg every two weeks as tolerated and based on the response of the levels of glucose in the blood. The maximum daily dose is 2550 mg given in three divided doses. If Glucophage XR tablets are used, the starting dose is 500 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg once daily or in two divided doses. Metformin should be taken with meals.

For pediatric patients 10-16 years of age, the starting dose is 500 mg twice a day. Dosage can be increased by 500 mg weekly up to a maximum dose of 2000 mg. Glucophage XR has not been studied in children.
DRUG INTERACTIONS: Cimetidine (Tagamet), by decreasing the elimination of metformin from the body, can increase the amount of metformin in the blood by 40%. This may increase the frequency of side effects from metformin.

PREGNANCY: There are no adequate studies in pregnant women. Most experts agree that insulin is the best treatment for pregnant women with diabetes.

NURSING MOTHERS: Metformin is excreted into breast milk and can therefore be transferred to the nursing infant. Nursing mothers should not use metformin.

SIDE EFFECTS: The most common side effects with metformin are nausea, vomiting, gas, bloating, diarrhea and loss of appetite. These symptoms occur in one out of every three patients. These side effects may be severe enough to cause therapy to be discontinued in one out of every 20 patients. These side effects are related to the dose of the medication and may decrease if the dose is reduced.

A serious--though rare--side effect of metformin is lactic acidosis. Lactic acidosis occurs in one out of every 30,000 patients and is fatal in 50% of cases. The symptoms of lactic acidosis are weakness, trouble breathing, abnormal heartbeats, unusual muscle pain, stomach discomfort, light-headedness and feeling cold. Patients at risk for lactic acidosis include those with reduced function of the kidneys or liver, congestive heart failure, severe acute illnesses, and dehydration. .

[Enchantress]

Summary of Interactions For Met and Herbs, Vitamins, Minerals, Food, and Alcohol

yalenewhavenhealth.org/Libra...hwid=hn-1437003

Glucophage?

Metformin is a drug used to lower blood sugar levels in people with non-insulin-dependent (type 2) diabetes.

Herbs
Summary of Interactions for Metformin

Depletion or interference Folic acid*

Vitamin B12
Adverse interaction Ginkgo biloba
Side effect reduction/prevention Calcium
Supportive interaction None known
Reduced drug absorption/bioavailability Guar gum*
Other (see text) DHEA

Magnesium

For the convenience of the reader, the information in the summary is categorized as follows: ?Depletion or interference? indicates the drug may deplete or interfere with the absorption or function of the supplement or herb. ?Adverse interaction? indicates that the supplement or herb used together with the drug may result in undesirable effects. ?Side effect reduction/prevention? indicates the supplement or herb may reduce the likelihood and/or severity of a potential side effect caused by the drug. ?Supportive interaction? indicates the supplement or herb may support or aid the function of the drug. ?Reduced drug absorption/bioavailability? indicates that the supplement or herb may decrease the absorption and/or activity of the drug in the body. An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Supplements
Dehydroepiandrosterone (DHEA)

Metformin has been reported to increase blood levels of DHEA-sulfate in at least two studies. 1, 2

Folic acid and Vitamin B12

Metformin therapy has been shown to deplete vitamin B12 and sometimes, but not always, 3 folic acid as well. 4 This depletion occurs through the interruption of a calcium-dependent mechanism. Supplementation with calcium has reversed this effect in a clinical trial. 5 People taking metformin should supplement vitamin B12 and folic acid or ask their doctor to monitor folic acid and vitamin B12 levels.

Magnesium

In a study of patients with poorly controlled type 2 diabetes, low blood levels of magnesium, and high urine magnesium loss, metformin therapy was associated with reduced urinary magnesium losses but no change in low blood levels of magnesium. 6 Whether this interaction has clinical importance remains unclear.

Guar gum

In a small, controlled study, guar gum plus metformin slowed the rate of metformin absorption. 7 In people with diabetes this interaction could reduce the blood sugar-lowering effectiveness of metformin. Until more is known, metformin should be taken two hours before or two hours after guar gum-containing supplements. It remains unclear whether the small amounts of guar gum found in many processed foods is enough to significantly affect metformin absorption.

Interactions with Herbs
Ginkgo biloba

In a preliminary trial, administration of Ginkgo biloba extract (120 mg per day) for three months to patients with type 2 diabetes who were taking oral anti-diabetes medication resulted in a significant worsening of glucose tolerance. Ginkgo did not impair glucose tolerance in individuals whose diabetes was controlled by diet. 8 Individuals taking oral anti-diabetes medication should consult a doctor before taking Ginkgo biloba.

Other Interactions
Food

Food interferes with metformin absorption. 9, 10, 11 Taking metformin with food can reduce the absorption of the drug. Therefore, metformin should be taken an hour before or two hours after a meal unless stomach upset occurs.

Alcohol

Lactic acidosis is a rare but serious side effect of metformin. Alcohol increases the production of lactic acid caused by metformin, increasing the risk of lactic acidosis. 12 People taking metformin should avoid alcohol or consult with their doctor before consuming alcohol.

[Enchantress]

Will I get Lactic Acidosis?

Although most every piece of literature on Met mentions it, LA is actually very uncommon. Documented cases of a normally healthy person without risk factors developing LA, are very rare, and the FDA is actually revising labels to reflect the rarity. And a large majority of people who develop it had specific risk factors for LA.

Stats vary, but the *highest* stat I have read on the subject is that 3 out of every 100,000 people perscribed Met develops a case of LA. So that's .003% of patients on Metformin...a very low number. And half of those cases are NOT fatal. So only .0015% of people on met for any period of time will die of LA.

LA is SIGNIFICANTLY more common in people with certain risk factors. These include:

A) Pre-existing cardiac disease

B) chronic pulmonary disease

C) severe liver disease

D) acute asthmatic attack

E) Patient over 80 years of age

F) Renal insufficency. *This risk factor is one of the biggest. Ninety percent of metformin is excreted unchanged by the kidneys and lactic acidosis typically occurs in patients with renal (kidney) insufficiency. So if you have had any degree of kidney problems in the past, you need to have liver tests done by your Dr before beginning metformin therapy.

G) patients on extremely high doses (higher than 2550 mg per day)

H) Patients severely dehydrated. Speak to your Dr if you are on a dieuretic.

I) Rapid ascent to high altitude can also be a risk factor.

J) LA is more common after certain surgeries. If you are having surgery involving iodinated contrast media or any other condition in which an acute decline in kidney function might occur (aggressive diuresis, excessive fluid loss from gastroenteritise etc) you can lower your risk significantly by discontinuing the drug a 24 hours to a week before your surgery. Speak with your surgeon about this if you are undergoing any procedures that may require discontinuing the drug.

K) LA is more common in people who drink moderate to heavy amounts of alcohol on Met.

If you are concerned about your risk factors or have concerns regarding LA, speak with your Dr.

Metformin-Associated Lactic Acidosis: www.medscape.com/viewarticle/417792_1

Searching for a Link - Met & LA:
www.ncbi.nlm.nih.gov/entrez/...4&dopt=Abstract

Study: Metformin patients had no higher incidence of LA than non-Met patients: www.diabetesincontrol.com/rosen/i186.shtml

Report: FDA revising Metformin labels to reflect that there were NO reports of lactic acidosis during more than 20,000 patient-years of exposure to metformin in clinical trials.

www.medscape.com/viewarticle/474836

What do the Symptoms of LA Look Like?

Symptoms of Lactic Acidosis (which can also be symptoms of other health issues): nausea, vomiting, altered level of consciousness, abdominal pain, severe thirst, severe lethargy and an increase in the depth and rate of your breathing.

www.psycheducation.org/hormo...ticacidosis.htm

[Enchantress]

Guidelines are strict, but data suggests a couple of drinks per week is perfectly fine on Metformin. But studies suggest some concerns with moderate to heavy drinking on metformin. This level of alcohol can actually delay a period due to it’s effect on hormones:

www.ncbi.nlm.nih.gov/entrez/...1&dopt=Abstract

Excessive amounts of alcohol can increase the effect of met resulting higher chances of hypoglycemia and lactic acidosis:
webmd.lycos.com/content/drugs/4/4052_143.htm

www.diabetesmonitor.com/metf-qa.htm

Drinking while on Met often causes increased nausea, abdominal discomfort and other side effects. So to counter this, some ladies discontinue Met when they are planning to drink in excess. By doing this, you increase your chances of hypoglycemia even further by leaving your insulin unregulated completely.

Many women on Met also find they get a ‘buzz’ a lot faster, so bear this in mind. This is because the liver is overworked due to the Met and processing the alcohol, so the alcohol moves through your bloodstream to other parts of your body..the alcohol moves to the brain because the liver can't process it. Symptoms of hypo look like those of drunkenness: confusion, slurred speech, dizziness, nausea and headache.

If you plan to drink, try to eat prior to (and while) drinking to keep your blood sugar up, limit your number of drinks, drink low sugar drinks if possible and drink as slowly as you can to keep from your liver being over-worked. If you use mixers in your drinks, choose ones that are sugar free, like diet soft drinks, diet tonic, club soda, seltzer, or water. This will help keep your blood sugar levels in your target range. Light beer and dry wines are good choices. They have less alcohol and carbohydrates and fewer calories. To make drinks last longer, try a "spritzer." Mix wine with sparkling water, club soda, or diet soda.

ANY consumption of alcohol should be discussed with your physican.

Diabetes Medication, blood sugar and alcohol: secure.lillydiabetes.com/Fo...als/alcohol.cfm

[natalie]

I just wanted to add, that although women frequently are advised to discontinue nursing with Met use, there is a growing body of studies that suppport its safety.

Obviously it is a very personal decision and should be done while consulting your doctor, but make sure (s)he is up on the latest studies!!!

Andecdotally, I have nursed for 13 months while using Mets and we have had no problems at all.

I will try to post some of the nursing studies in the near future!

[Dara]

Transfer of metformin into human milk

neonatal.ttuhsc.edu/lact/Metformin.pdf


Aims/hypothesis. The aim of this study was to characterize the milk-to-plasma ratio and infant dose for metformin in breastfeeding women, and to measure plasma concentrations and assess any effects in their infants. We hypothesized that metformin used by mothers is safe for their breastfed infants.

Methods. Seven women taking metformin (median dose 1500 mg orally daily) and their infants were studied. Metformin concentrations in plasma and milk were measured by high performance liquid chromatography. Infant exposure was estimated as the product of estimated milk production rate and the average concentration of the drug in milk and also expressed as a percentage of the weight-normalized maternal dose.

Results. The mean milk-to-plasma ratio for metformin was 0.35 (95%CI 0.2–0.5). The mean of its average concentrations in milk over the dose interval was 0.27 mg/l (0.15–0.39 mg/l). The absolute infant dose averaged 0.04 mg·kg–1·day–1 (0.02–0.06 mg·kg–1·day–1) and the mean relative infant dose was 0.28% (0.16–0.4%). Metformin was present in very low or undetectable concentrations in the plasma of four of the infants who were studied. No health problems were found in the six infants who were evaluated.

Conclusions/interpretation. The oncentrations of metformin in breast milk were generally low and the mean infant exposure to the drug was only 0.28% of the weight-normalized maternal dose. As this is well below the 10% level of concern for breastfeeding, and because the infants were healthy, we conclude that metformin use by breastfeeding mothers is safe. Nevertheless, each decision to breastfeed should be made after conducting a risk:benefit analysis for each mother and her infant.

[Diabetologia (2002) 45:1509–1514]
Keywords Metformin, human milk, milk-to-plasma ratio, infant dose, PCOS.
Received: 3 May 2002 / Revised: 12 July 2002
Published online: 25 September 2002