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Aug 18, 2008

One of the Most Effective Diabetes Drugs

Amy Campbell

You may recall that I recently wrote a series on various medicines and how they can affect your diabetes (see "The Ups and Downs of Meds and Diabetes [Part 1]" as well as Part 2, Part 3, Part 4, and Part 5). One kind reader, who happens to be a nurse, asked me to devote a post to metformin with regard to its effects on kidneys and special considerations to keep in mind with this drug.

I wrote about metformin back in December 2006 (was it that long ago?) and its link to vitamin B12 deficiency (see "Metformin and Risk For Vitamin B12 Deficiency"). But there are other important facts to know about this very popular diabetes drug.

Raise your hand if you take metformin. OK, obviously I can't see you, but I'll wager that many of you reading this are on this medication. Metformin is the generic name for Glucophage, Glucophage XR, Glumetza, Fortamet, and Riomet. It also comes combined with other diabetes medications, including glyburide (in Glucovance), glipizide (in Metaglip), rosiglitazone (in Avandamet), pioglitazone (in Actoplus Met), sitagliptin (in Janumet), and repaglinide (in PrandiMet).

I've read that approximately 35 million prescriptions were written for metformin in 2006, making this one of the top 10 best selling generic drugs. And you may not be aware that the American Diabetes Association, in its 2006 practice guidelines for health-care professionals, recommended metformin over sulfonylureas as the first drug of choice for people with Type 2 diabetes. This really isn't surprising. Metformin has a long track record for being safe and causing relatively few serious side effects—plus, it also works! Chances are, if you have Type 2 diabetes and need to start on medication, your health-care provider will recommend you take metformin.

How It Works
Just a quick review in case you're not sure what metformin does. Metformin works by:

Reducing the amount of glucose released by your liver (and your liver regularly releases glucose); and
Helping the insulin in your body work better (i.e., increasing insulin sensitivity).

Metformin doesn't cause your pancreas to secrete insulin, as do sulfonylureas, so it's very unlikely that you will experience hypoglycemia (low blood glucose) with metformin alone; however, if you take a sulfonylurea or insulin along with metformin, you may get hypoglycemia.

Side effects are usually temporary, and consist of gas, nausea, vomiting, and/or diarrhea. Some people have side effects, some never do. And if you can "stomach" metformin for the first month or so, you may end up losing weight (another benefit for many people).

Metformin isn't meant for people with Type 1 diabetes, although it has been known to be given "off label" to people with Type 1 who also have insulin resistance.

Things To Keep in Mind

Lactic acidosis: Lactic acidosis is a rare but extremely serious condition that occurs in about 1 out of every 30,000 people who take metformin. Symptoms include weakness, shortness of breath, abdominal pain, and muscle pain. People at increased risk for lactic acidosis include those with kidney or liver problems, congestive heart failure, alcohol abuse, or dehydration. Lactic acidosis may also occur if metformin is taken during X-rays with dye and surgery; for this reason, metformin usually needs to be stopped 48 hours before these procedures. Always talk with your health-care provider if you take metformin and are scheduled for an X-ray, CAT scan, or for surgery.

In addition, metformin should not be used in people with a creatinine clearance of less than 30 ml/minute, and used with great caution if the creatinine clearance is between 30 and 50 ml/minute (creatinine clearance is a test that measures how well your kidneys are working). So, if you have diabetic kidney disease, metformin may not be the first drug of choice for you.

Irregular menstrual periods: Metformin is used to induce ovulation in women with polycystic ovary syndrome (PCOS), a condition that can lead to an irregular menstrual cycle.

Gestational diabetes Metformin is now deemed to be safe in women with gestational diabetes. Women with gestational diabetes traditionally had to take insulin during their pregnancy. Metformin (and also glyburide, brand names Micronase, DiaBeta, and Glynase), are now two other options.

Prediabetes: Although not formally approved by the U.S. Food and Drug Administration (FDA), metformin has been given with success to people who have prediabetes, and, in fact, was used in a major study called the Diabetes Prevention Program to help prevent diabetes.

Children: The incidence of Type 2 diabetes in children is escalating, and while, of course, lifestyle changes are critical, metformin should be the first drug of choice, if indicated.

One of the physicians I work with calls metformin the "best medication for treating Type 2 diabetes." So, if you are one of the many who take metformin, I hope that's the case for you!

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metforom works great for me i have type2

Posted by: mr.fff | Aug 20, 2008 12:33 PM

I used Metaformin for years and it always worked very well on my type 2 diabetes.
Then out of the blue.I started have diarrhea, then uncontrollalbe diarrhea, at times unable to leave the house.
I finally had to stop taking it for this reason.
It was back to Insulin for me as no other oral medication ever worked as well as the Metaformin.

Posted by: Raccary | Aug 20, 2008 01:55 PM

Interesting options for the survey. What about those who used to take it for Type 2 diabetes and found it did not help and are now on insulin?

Posted by: Mike | Aug 20, 2008 02:32 PM

Good point, Mike--I didn't think to include an option for having taken metformin in the past but not anymore. I guess that the closest response would be "No, I have Type 2 diabetes and do not take metformin," though that certainly doesn't tell the whole story.

Posted by: Tara Dairman, Web Editor | Aug 20, 2008 02:57 PM

Dear Tara. The survey should include an option that I have tried but had to quit the drug. Many people get quite sick on it.

Posted by: CalgaryDiabetic | Aug 20, 2008 03:57 PM

I, too, am on Metformin after diet and exercise alone didn't lower my blood sugar. My question is this: which is the best way to take metformin, with or without food and are there any specific times of the day to take it? I take it twice a day and have been told just to take it twice a day at any time of the day. What do you suggest?

Posted by: Kris | Aug 20, 2008 05:34 PM

I've taken metformin for many years. First by itself, then with glyburide. At first it made me nauseous and had other side effects. Gradually those went away. Now I don't notice any side effects. When I started my new diet and exercise regimen I began to have frequent hypoglcemic episodes. So, my doctor stopped the glyburide and now I take only the metformin. My A1c is down so I don't have to use anything but the metformin.

Posted by: budgetboy | Aug 20, 2008 06:32 PM

I have type 2 diabetes and have used metformin 500mg for years without any problems. But this past year I started to have higher blood sugar levels so my doctor gradually raised the dosage to 2000mg a day and it seems to be working fine again.

Posted by: grammasmiles | Aug 20, 2008 08:16 PM

I found for many years that Metformin was very effective in controlling my glucose. I did experience some of the side effects listed above.

As a follow-up to the 2006 article re: B-12 Deficiency, I am finding many long term users are experiencing fatigue. Whether or not they have developed pernicious anemia, I don't know. However, B-12 has been effective for most.

Pernicious Anemia is serious stuff. Back in the day (way back)it was a fatal condition.

In December, 2007 I was taking Actos, 200 mg of Metformin,and 70 units of Insulin per day. Withing 5 weeks after starting B-12 supplements, I was off insulin (as in ZERO)and Actos.

I am now down to 750mg of Metformin. Still a very good med but please, PLEASE ask you Doc for a CBC to check your B12. It is not a normal part of your A1C protocol.

Posted by: sh10492 | Aug 20, 2008 08:44 PM

My husband has type 2 diabetes and just recently started having a lot of diarheaa.He was diagnosed last year and was put on metformin.He is still on it plus glimeperide now as well.He takes the metformin twice a day and a half pill of the other twice a day.Can this be the cause of his diarrhea?Other than that he seems to be doing okay with the diabetes its just that the bathroom going all the time concerns me.

Posted by: mary | Aug 21, 2008 01:43 AM

I was DX-d with Type II Diabetes in May of 2008. However, I had it a lot longer than this. The symptoms were all there but my primary doctor never took me serious.

On Feb 21, 2008, I fell and broke my wrist. The paramedics measure blood glusos and asked me if I was diabetic, I told them "NO, I had never been diagnosed". My blood sugar count was over 400....

When I finally got DX'd, the doctor RX'd me Medformin 1000 X twice a day.

So far, so good.No more side affects than I already had.

I have Fibromyalgia which mimics diabetes.

I had part of my right lung removed in 2004, it was cancer, but thank God, I was cured of that.

When I was told I had cancer, I was calm, no big deal...I would either get well or die.

But when they told me I had diabetes, I went into shock, remembering all the horror stories about diabetics losing their digits and or limbs or having to take all kind of treatments etc...i.e. kidneys.

So yes, the Medformin is saving me a lot of grief, I am just glad they have a medicine that works

Maybe this was more then y'all wanted to know but I wanted to share with you , how much better I feel now since I am on Medformin.

Posted by: SUNNIE | Aug 21, 2008 02:07 AM

I've been using metformin and so far it's the best drug out there.

Posted by: Bahamut | Aug 21, 2008 12:25 PM

Thanks to all for sharing your thoughts and stories. Sounds like, for most of you, metformin has been a big success! Also, I wanted to add that vitamin B12 deficiency is a definite issue for long-term metformin users. This isn't measured in a standard CBC blood test, so it's worthwhile talking to your healthcare provider about this and whether you should have your B12 level measured. This would also be a blood test separate from a CBC.

Posted by: acampbell | Aug 21, 2008 04:56 PM

I am seventy and have been diabetic since the mid-1980s. I have been on insulin since 1995. I had taken metformin for years but in the past couple of years, had to stop taking it because of severe intestinal discomfort. I have IBS, and this aggravated it considerably. For the first few years I was on this drug I took the original Glucophage and got along fine. I began having problems when the prescription was switched to generics. I have had similar problems with other drugs. Something used (perhaps in the base) to make the generic drug seems to be causing the problem. My medicare supplement will not pay for the more expensive glucophage, so I have just increased my insulin and no longer take the oral drug. I can't help feeling that the pharmaceutical and insurance industies are ruling our lives.

Posted by: LAW | Aug 21, 2008 05:40 PM

I've been using metformin for about two years and have not had any problem with it. The drug that gave me all the problems was Actos.

Posted by: carolena | Aug 21, 2008 07:41 PM

I have type 2 and take 1000mg Metformin in the am and 1000mg in the pm. In addition I take 50mg Starlix before each meal and this combination works perfectly for me - provided I remember to take the Starlix each time.

Posted by: RBD | Aug 21, 2008 11:41 PM

Hi Kris,
Metformin is intended to be taken with a meal, so if you take this twice a day, you'd likely take it right before you eat breakfast and then right before supper. The extended release version of metformin is taken once a day, usually with the supper meal. However, it's a good idea to check with your physician as to the best time for you to take metformin.

Posted by: acampbell | Aug 22, 2008 08:07 AM

Hi Mary,

It's possible that the metformin is causing his diarrhea. However, there are many other causes of diarrhea, ranging from bacterial and viral infections, to parasites, to food intolerances (such as lactose intolerance, celiac disease), to intestinal disorders (Crohn's disease, ulcerative colitis). I'd suggest he talk to his physician about this. Perhaps he can decrease the dose, temporarily, to see if this makes a difference.

Posted by: acampbell | Aug 22, 2008 03:53 PM

I am also on Metformin. I take the Extended release version and the side effects are practically none. The regular metformin did give me the stomach distress horribly, in fact I dealt with it for almost 6 months.

I was handling with diet and exercise for years but ened up with Metformin and it controls the highs and lows much better and helps keep me in the range my doctor and I both are comfortable with.

Posted by: MzizGayle | Aug 24, 2008 07:07 AM

I have been on Merformin 500 x2 for 3 years. The first year I lost 75 lbs. and have maintained that weight for the last 2 years. Also at the end of the first year my a1c was 6.0 and is now 5.1 I have been very satisfied with the way metformin has worked for me.

Posted by: Joan | Aug 24, 2008 11:20 PM

Hi Chris & Acampbell
Regarding when to take your Metformin, actually a diabetic nurse suggested I take mine (2 500 daily) in the evening before I go to bed I have done this for about 7 years and my A1C is 5.2.

Posted by: ColoradoSprings | Aug 27, 2008 04:26 PM

Hi ColoradoSprings,
Thanks for sharing. It can make sense for people who take metformin to take most or all of their dose in the evening, especially if their fasting glucose levels tend to be high. The liver tends to put out more glucose in the early morning hours, so this is the perfect time of day to have metformin on board. It's a good idea for people who take metformin to talk with their provider about the best time(s) to take their doses.

Posted by: acampbell | Aug 28, 2008 07:41 AM

Re: the concern about the risk of lactic acidosis associated with using metformin.

Perspective is an important factor in evaluating this risk, which seems quite small.

It has been published in several studies that death from lactic acidosis is higher among those who do not take metformin than among those who do.

In references below, please note that those portions within { } are my comments.

Classification of Some Causes of Lactic Acidosis (Cohen & Woods, 1976) {Article Last Updated: Mar 27, 2007}

Type A Lactic Acidosis : Clinical Evidence of Inadequate Tissue Oxygen Delivery

Anaerobic muscular activity (eg sprinting, generalised convulsions)

Tissue hypoperfusion (eg shock -septic, cardiogenic or hypovolaemic; hypotension; cardiac arrest; acute heart failure; regional hypoperfusion esp mesenteric ischaemia)

Reduced tissue oxygen delivery or utilisation (eg hypoxaemia, carbon monoxide poisoning, severe anaemia)

Type B Lactic Acidosis: No Clinical Evidence of Inadequate Tissue Oxygen Delivery

type B1 : Associated with underlying diseases (eg ketoacidosis, leukaemia, lymphoma, AIDS)

type B2: Assoc with drugs & toxins (eg phenformin {a biguinide, but NOT metformin***}, cyanide, beta-agonists {some blood presure medications}, methanol, nitroprusside infusion, ethanol intoxication in chronic alcoholics, anti-retroviral drugs)

type B3: Assoc with inborn errors of metabolism (eg congenital forms of lactic acidosis with various enzyme defects eg pyruvate dehydrogenase deficiency)

Note: This list does not include all causes of lactic acidosis.

http://www.emedicine.com/med/topic1253.htm

*** Phenformin, a hypoglycemic agent used for type 2 diabetes, was withdrawn from the U.S. market in 1977 due to a reported rate of lactic acidosis of 40 to 64 cases per 100,000 patient-years. Metformin has been implicated as a cause of lactic acidosis because it is a related biguanide. However, metformin, unlike phenformin, enhances glucose oxidation without subsequently affecting fasting lactate production in peripheral tissues. Metformin has been in use for more than 40 years worldwide and has the positive effects of weight reduction and stabilization in addition to reductions in diabetes-related morbidity and mortality as reported by the U.K. Prospective Diabetes Study in the Sept. 12, 1998, issue of The Lancet. However, the true incidence of metformin-associated lactic acidosis is not known. Case reports have included patients with pre-existing renal or hepatic failure, both of which are contraindications to metformin use, and patients with hypoxia or hypoperfusion, which predispose to lactic acidosis. To date, 330 cases of lactic acidosis have been reported in such diabetic patients, according to the spring 1992 issue of the Archives of Medical Research. In clinical practice, 54% to 73% of patients receiving metformin have at least one contraindication to treatment, researchers report in the June 1997 issue of Diabetes Care. For example, in one cross-sectional study, 19% of patients receiving metformin after hospital admission had renal insufficiency.

http://www.medscape.com/viewarticle/464991?mpid=21795
----------

http://jasn.asnjournals.org/cgi/content/full/12/suppl_1/S15
{in this article, go down to the section "The Biguanide Dilemma" for specific info on metformin}

----------

http://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.php

Posted by: marcie | Aug 30, 2008 02:50 PM

Hi Marcie,
Thanks for sharing all of this. Lactic acidosis is certainly a possible side-effect of taking metformin, but the incidence isn't well-known, and is likely fairly low, although it's more likely to occur in critically ill patients. Anyone who takes metformin needs to be aware of possible signs and symptoms, and should they occur, to seek medical attention immediately.

Posted by: acampbell | Sep 02, 2008 03:02 PM

Hello,

Metformin is the ticket. When I was originally diagnosed, my level was over 500 - I thought I was pregnant. Well, my doctor gave me the 500 metformin. It didn't do anything, so he gave me glipizide with it - worked wonders to bring my level down. so i stopped the metformin and stayed on the glipizide. Well, my feet started swelling
and i gained another 15 pounds - but my sugar was under perfect control. Perfect. So when i got my sugar level under control, i was tired of the extra water and weight; i went on metformin only -which doesn't cause weight gain. It causes diahrea at first but your body will adjust after about 2 months of taking it. If my sugar level gets too high, i will take like a 1/4 tab of the glipizide, which pulls everything immediately back in control; but makes my feet swell for a couple of days. Can you imagine 1/4 glipizide does this - it must be really strong - after that, my sugar is back in control and I only use a 1/4 tablet when necessary. Hope this helps. Stay on the metformin and use the glipizide if needed for excessively high readings.

Posted by: shiney | Sep 11, 2008 03:46 AM

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