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Metformin (Glucophage) Side Effects & Complications

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This fascinating compound was discovered nearly a century ago. Scientists realized that it could lower blood sugar in an animal model (rabbits) as early as 1929 but it wasn't until the late 1950s that a French researcher came up with the name Glucophage (roughly translated as glucose eater). The FDA gave Glucophage (metformin) the green light for the treatment of type 2 diabetes in 1994, 36 years after it had been approved for this use in Britain.

Glucophage lost its patent protection in the U.S. in 2002 and now most prescriptions are filled with generic metformin. This drug is recognized as a first line treatment to control blood sugar by improving the cells' response to insulin and reducing the amount of sugar that the liver makes. Unlike some other oral diabetes drugs, it doesn't lead to weight gain and may even help people get their weight under control.

Starting early in 2000, sales of metformin were challenged by a new class of diabetes drugs. First Avandia and then Actos tested metformin for leadership in diabetes treatment. Then Avandia lost its luster because of a link to heart attacks and strokes and now sales are miniscule because of tight FDA regulations. Actos is coming under increasing scrutiny as well. The drug has been banned in France and Germany because of a link to bladder cancer. The FDA has also required Actos to carry its strictest black box warning about an increased risk of congestive heart failure brought on by the drug.

This all means that metformin has regained its reputation as the best bang for the buck when it comes to type 2 diabetes management. The American College of Physicians has recommended metformin as the first line of treatment when lifestyle changes (diet, exercise and weight loss) have not led to adequate blood glucose control. That may be why nearly 50 million metformin prescriptions were dispensed last year.

Despite all the warm, fuzzy feelings about metformin for type 2 diabetes, there are some caveats. This drug does cause a number of side effects, especially when it comes to the gastrointestinal tract. They can be especially bothersome during the first few weeks of treatment. After several weeks, however, the digestive symptoms may fade away. If they recur, however, notify your doctor immediately as they could be symptoms of lactic acidosis (see below). Here is a list of adverse reactions to watch out for:

METFORMIN SIDE EFFECTS





• Heartburn


• Stomach ache


• Diarrhea


• Gas


• Headache


• Nausea


• Loss of appetite


• Weakness


• Rash


• Lactic acidosis (symptoms may include irregular heart rate, nausea, stomach pain, lethargy, anxiety, low blood pressure and rapid heart rate) Notify your physician immediately if you notice any of these symptoms!

These side effects may seem daunting, but most people tolerate metformin quite well. The drug can be dangerous for people with kidney disease, however. They should not take the drug, and everyone on metformin should have their kidney function monitored regularly (at least once a year). People with congestive heart failure should not take metformin either.

There is an unexpected bonus to metformin therapy. There is growing evidence that this drug has an anti-cancer effect that may both prevent cancers from developing and spreading. In particular there are data suggesting that metformin may lower the risk of developing breast cancer, liver cancer, pancreatic cancer and colorectal cancer in people with diabetes and that the overall risk of developing cancer in such patients is substantially lower.

A final word of caution, though. There are some nutritional consequences of metformin therapy. Here are some stories from readers. Please add your own comments about metformin treatment below theirs.

Q. I have read that metformin can cause a deficiency of Vitamin B12. I have not been able to find again the source of this information and would like your input.
Abigail

PEOPLE'S PHARMACY RESPONSE: This is from the prescribing information at DailyMed, identical to what is published in the PDR:

"Vitamin B12 Levels: In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on metformin and any apparent abnormalities should be appropriately investigated and managed (see PRECAUTIONS: Laboratory Tests).
Certain individuals (those with inadequate Vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal Vitamin B12 levels. In these patients, routine serum Vitamin B12 measurements at two- to three-year intervals may be useful."

+++++++++++++++++++

Q. My husband took metformin for years with no known side effects. Then his kidney functions started to deteriorate so he was seen by a specialist who immediately took him off metformin. He said that drug was very hard on kidneys and anyone who had any variations in kidney functions should not be taking it.

A. As mentioned above, kidney function must be monitored regularly to prevent just such a complication.

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Q. I am suffering from such severe diarrhea I am sometimes afraid to leave the house. I also have bad gas and bouts of abdominal pain. I suspect the metformin I take for diabetes, but my doctor says my symptoms are not from my medicine.

The Prevacid I take for my heartburn isn't helping enough to justify the expense. I am also experiencing pain and tingling in my toes.

A. Metformin (Glucophage) can cause diarrhea, nausea, heartburn, flatulence and stomachache. Acid-suppressing drugs like lansoprazole (Prevacid), omeprazole (Prilosec) or esomeprazole (Nexium) won't solve the problem completely and may interfere with absorption of vitamin B12.

Metformin is also linked to reduced levels of vitamin B12. Because this vitamin is crucial for nerve function, deficiency can contribute to numbness, tingling or pain of the toes, feet or fingers, trouble walking, memory problems, depression, confusion and burning tongue.

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22 Comments

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Re: Metformin, what dosage prolonged in how long before the damage sets in, kidney wise?

Metformin has taken some time to get used to. At first, with a twice daily dose, it caused sudden diarrhea that was inhibiting my daily life. I am now on once-a-day insulin and take a low dose of metformin(1/2 tablet or one whole) only at night. I skip a dose if I know I have a morning appointment because the sudden loose stools continue. I only wish that my doctor had emphasized to watch for the gastric symptoms.

Metformin caused me increasingly severe diarrhea, to the point where I was having a dozen or more episodes a day, and lost 14 pounds in two weeks. I had been on Fortamet, but asked to be switched to generic metformin because of the cost. I also had daily diarrhea with Fortamet, but it was much, much worse when I took the generic form. I'm now on a slow-release form of Fortamet, but still have two or three bouts of diarrhea almost every day.

Metformin has caused my husband to lose weight and his appetite. He is nothing but skin and bones from it. He has stopped taking it as of yesterday.
He has type 2 diabetes.

I took four doses of Metformin over the course of 2 1/2 days and then developed excruciating pain while out walking to the point that I felt like I might not be able to get home. It was in my lower back and up thighs. (I'm 55 and walk regularly.) I did a google search and found others who stopped after developing pain. Has anyone on here?

I was diagnosed with pcos 3 years, few months later I was diagnosed with pylonepritis and was treated with gentamicin, but I still felt symptoms of pylonepritis and my doctor said my kidney was still patchy even after the treatment. She advised I should take plenty of water. I have been trying to achieve pregnancy and I was placed on metformin 1500mg, please will metformin have any effect on my kidneys even with pylonephritis? I still feel pain in my flank and abdominal discomfort and bloating. Thanks.

I've been taking Metformin for about 2 years and during that time Ive lost a few pounds. I also feel tired after about 2 hours. At first I couldn't figure out why I was so tired all the time and then I noticed that it was only after I took this medication. Since that time my doctor has placed me on the slow release version of the medication. But my big issue now is heartburn. I've have been experiencing this terrible heartburn to the point that I feel like I need to go to the ER if I don't get any type of relief. I believe that it maybe one of the side effects. I have to do some more research and see what happens.

Has anyone heard about any heartburn side effects??

I am wondering if Glucophage can increase anxiety.

People's Pharmacy response: this is not a common reaction to metformin.

I have been on Metformin for 3 years now and I have constant diarrhea, it has gotten so bad that I am having absorption issues. My vitamin D levels are very very low (22.3) when normal range is 30.0 - 100.0.

I have been complaining to my doctor about this but it seems to go in one ear and out the other with him. I know time to find a new doctor!! I did not want to stop the metformin as it seems to be the best med out there for type II diabetes. Is there any other drug that works as well as Metformin? Worst part is I have not lost any weight, at least that would have been a bonus!

I am on metformin for months now and noticed low back pain, buttocks thigh to the leg pain, just wandering if metformin is causing it, I have seen ortho, physical therapist, acupuncturist, massage therapist and Chiro but still suffering from severe pain anyone with same problem?

I've been taking a very low dose of metformin for a little over a month now. It never seems to bother me of I take it with the biggest meal of my day. But if I don't have enough food with it, the diarrhea is so severe I'm scared to leave the house. :/

I'm on my fourth day of Metformin 500mg once a day. I immediately noticed lower back pain, mostly down through my buttocks and my left leg. The pain is like an ache, feels as if I have pulled a muscle. Today I was able to definitely associate the Metforminn with the pain. The pain occurred within an hour of taking the metformin. Am also noticing a burning sensation on the bottom of my feet. I was hoping that these side effects would go away after a short time on metformin, but after reading the comments on this forum, have serious doubts. My A1c has never been higher than 6.1 but I was gaining weight like crazy and feeling very sluggish/extremely tired and my iron and vitamin D levels continuously low so I requested to be put on metformin. I now wonder if I will be able to continue with this medication?

I have been taking Metformin 500MG for a year for my diabetes T2. It appears now that it is causing me low blood pressure so I have been advised to reduce the dosage to half a day for the next month. Anyone have similar problems?

I have type 2 diabetes and was diagnosed a year ago. Ever since I have been on metformin 500 mg three times a day. For over six months my stool has been light green. Every thing else is normal. Are these light green stools caused by metformin?

My husband has type 2 diabetes, and has been on 20mg glycide per day plus 1000 mg of metformin per day. His kidney function has dropped to stage 3 kidney failure. His Dr has taken him off the metformin, but has not replaced it with anything else. Can anyone recommend another medication so we can ask the Dr. about it. The glycide alone is not keeping his BS down. Insulin injections would affect his job, so we are trying to avoid this.

I am a T2 diabetic patient and had been on metformin, 500mg, morning and evening, for about 3 years (just stopped the usage). I noticed that the more I use it ,the more my muscles relaxed and sagged even with 1hr (at times 2hrs, morning and evening when I had time). My muscles and skin were no more firm and I started looking much older than my age even with my serious routine exercise!I stopped for about 3wks now and have been on a very low carb (veg and protein) diet. My muscles are now much firmer and am looking younger that is very noticeable! I am worried now about the effect of much protein on my kidney in future! Thanks. May.

I have been taking Metformin for 20 yrs now and the worst side effect I got was Gerd. I take prescription vitamin B12 and one weekly vitamin D for my kidneys because I went into renal failure because of the Metformin. I still take it but at a lower dose and the vitamins help.

I just started taking 500 mg of metformin once a day this past week. I am also a heart failure patient. My cardiologist said it was ok to try this medicine. I am not so sure. My A1C was 8.1 in march, down from 9 last year at this time. Anyone else on this that's a heart failure patient?

After only 3 months of er metformin the muscle aches were so bad could not function was hospitalised so much pain couldn't use my hands. It felt like I had been kicked all over. I'm off them now. So far for just 2 weeks still got muscle problem but think it will take a while to go back to normal.

I was placed on 500mg of Metformin for Type II diabetes. My A1C has never been higher than 6.0. After taking the Metformin for a year I developed weakness in my legs, bone pain in my hips and severe diarrhea. I stopped taking the Metformin and these problems went away. I resumed the Metformin and the problems returned. I don't care what any doctor tells me, any medication that makes your problem bigger can't be good. I believe the risks outweigh the benefits.

I've had diabetes 2 for over ten years now and have been on insulin for 4 years. Since I was put on metformin I have been having diarrhea and I complained to my endocrinologist and he said its the best tab for me. And he said that its probably taking out lots of excess sugar in the stool that it helps control the diabetes for me. But it scares me when I am outside and I have to find a toilet and I have been worried that accidents might happen while trying to find one. Times when I didn't even want to go out, or sometimes i go out with my grandkids and it is very inconvenient to run looking for a rest room. I go out with friends and I have to find a place two or three times, its embarrassing. Is there any other tablet without that side effect?

I have been taking metformin for months now, but lately I have severe aches all over my body, not only that I am burning from the inside and I feel blisters forming, I stopped, but is there anything I can do?

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