metformin - side effects - comments?

Question

anyone with type 1 diabetes using metformin? My mum is 75 and has just had her insulin reduced and been prescribed 4 x 500mg daily. Her doctor is using this to counteract insulin resistance. Any comments on side effects etc?

Answer 1

Side Effects of Metformin (Glucophage)

MALAISE. 10%- 25% of women who take Glucophage just don't feel well. They experience a general malaise, fatigue and occasional achiness that lasts for varying lengths of time. Malaise a signal for the physician to closely monitor body systems affected by metformin, including liver, kidneys, and GI tract. A blood count should be taken from time to time, because metformin can induce B vitamin insufficiencies that can lead to a form of anemia.

GI DISTURBANCE. About one third of women on metformin experience gastrointestinal disturbances, including nausea, occasional vomiting and loose, more frequent bowel movements, or diarrhea. This problem occurs more often after meals rich in fats or sugars. The symptoms lessen over time, so if you can tolerate the GI upset for a few weeks, it may go away. Some women have found it helps to start with a very low dose and gradually increase it. One "benefit" of these unpleasant symptoms is that you find yourself eating less and thus losing some weight.

VITAMIN B12 MALABSORPTION. Of patients who take this drug, 10%-30% show evidence of reduced vitamin B12 absorption. A substance formed in the stomach called "intrinsic factor" combines with B12 so that it can be transferred into the blood. Metformin interferes with the ability of your cells to absorb this intrinsic factor-vitamin B12 complex.(12)

Over the long term, vitamin B12 insufficiency is a significant health risk. B12 is essential to the proper growth and function of every cell in your body. It's required for synthesis of DNA and for many crucial biochemical functions. There is also a link between B12 insufficiency and cardiovascular disease.

At least one study raises the concern that even if metformin is withdrawn, the vitamin B12 malabsorption may continue in some people.(13) The apparent cause is continued problems with availability of intrinsic factor, which is required for B12 absorption.

ELEVATED HOMOCYSTEINE. People who take Glucophage tend to have higher homocysteine levels.(14) Women with PCOS also tend to have elevated homocysteine.(15)

Homocysteine is an amino acid in the blood. A normal amount is OK. But an elevated level means that your metabolic processes are not working properly. Elevated homocysteine is associated with coronary artery disease, heart attack, chronic fatigue, fibromyalgia,(16) cognitive impairment.(17), and cervical cancer. (18)

Vitamin B12, along with vitamin B6 and folic acid (another B vitamin), is responsible for metabolizing homocysteine into less potentially harmful substances (19). Therefore, when metformin reduces absorption of vitamin B12, you lose one of the nutrients needed to reduce homocysteine and thus reduce your risk of cardiovascular disease.

ELEVATED HOMOCYSTEINE & PREGNANCY COMPLICATIONS. Pre-eclampsia is a complication of pregnancy characterized by increasing blood pressure and edema. If left untreated, pre-ecampsia can lead to eclampsia, a serious condition that puts you and your baby at risk. In a study conducted at the Center for Perinatal Studies at Swedish Medical Center in Seattle, a second trimester elevation of homocysteine was associated with a 3.2 fold increased risk of pre-eclampsia.(20)

The Dept. of Obstetrics and Gynecology, Nijmegen, The Netherlands, reviewed a series of studies on the linkage between elevated homocysteine and early pregnancy loss. They concluded that high homocysteine levels are a risk factor for recurrent early pregnancy loss.(21)

Ovarian follicular fluid contains detectable amounts of homocysteine along with B12, B6, and folic acid. The follicular fluid provides nourishment to the egg by facilitating transport of nutrients from blood plasma. High levels of homocysteine as well as an insufficiency of B vitamins may adversely influence the process of fertilization and early fetal development.(22)

NOTE: We are suggesting that elevated homocysteine, not metformin itself, could contribute to pregnancy complications in some women. However, metformin does contribute to increased homocysteine levels.

PREGNANCY WARNING. Many women use metformin in their pursuit of a successful pregnancy. However, Glucophage is a category B drug, meaning its safety for use while pregnant has not been established. It is found in breast milk so it's not advisable to breast feed while taking Glucophage.

ANEMIA. By preventing optimal absorption of vitamins B12 and folic acid, metformin could induce or contribute to megaloblastic anemia.(23) Megaloblastic anemia occurs when your bone marrow doesn't have enough B vitamins to manufacture red blood cells. Your bone marrow then releases immature and dysfunctional red blood cells into circulation.

Although anemia is not common among people taking metformin, it remains a risk for those whose B12 and folic acid levels were already low when metformin therapy was started.

LIVER OR KIDNEY PROBLEMS. If you have liver or kidney problems of any kind, metformin could pose a problem, because it alters liver function and is excreted through the kidneys. A healthy liver and kidneys will improve your outcome with metformin. Liver and kidney function should be assessed before starting metformin and rechecked at least once a year while taking it. A blood chemistry screen and a complete blood count will tell your physician how well your system is doing with this drug.

MULTIPLE MEDICATIONS. You may be at risk for health problems or symptoms if you take metformin in addition to other medications. The more drugs you take, and the higher the dosage, the greater the probability there will be some kind of interaction between the drugs or some unexpected effect from the combined drugs. The effect of combined drugs also depends on the state of your health, your genetic uniqueness, and your diet and lifestyle. Always consult with your doctor if you add or change any medication, or if you develop any symptoms.

HAIR LOSS. Metformin may contribute to male pattern hair loss at the temples and top of head. Although there's nothing in the medical literature to support this linkage, some women have reported that hair loss was made worse by metformin.(24)

LACTIC ACIDOSIS. About 3 of every 100,000 people who take metformin will develop a medical emergency called "lactic acidosis". Lactic acid is a metabolic byproduct that can become toxic if it builds up faster than it is neutralized. Lactic acidosis is most likely to occur in people who with diabetes, kidney or liver disease, multiple medications, dehydration, or severe chronic stress.

Lactic acidosis can gradually build up. Symptoms to watch for include a need to breathe deeply and more rapidly, a slow, irregular pulse, a feeling of weakness, muscle pain, sleepiness, and a sense of feeling very sick. Treatment requires intravenous administration of sodium bicarbonate. Contact your doctor or go immediately to a hospital emergency room if you have these symptoms.

BILE ABNORMALITIES. Bile is produced by the liver, stored in the gallbladder, and secreted into the intestines in order to absorb fats into the bloodstream. One possible reason for the GI problems is that metformin reduces normal reabsorption of bile from the intestines back into the bloodstream, which causes elevated bile salt concentrations in the colon.(25) Most studies suggest that colonic bile salts cause free radical damage to DNA and may contribute to colon cancer.(26,27)

In addition, bile acids may stimulate cells in the colon to produce leukotriene B4 (LTB4), a highly inflammatory substance. LTB4 would be a contributor to any intestinal inflammatory condition.(28) Byproducts of bacterial action on bile salts may lead to intestinal cell damage and absorption of "foreign" molecules such as food or bacteria particles into the bloodsteam, possibly causing allergies and other immune responses.(29)

Moreover, many PCOS women have switched to a high-protein diet. If that protein consists of beef and other meats, bile acid concentration in the intestines is increased.(30) A diet high in meats is also linked to a higher risk of colon cancer.

CONSULT WITH YOUR PHYSICIAN TO MINIMIZE RISK. Your physician should always do a thorough medical history and metabolic assessment before putting you on metformin. You should be re-checked at least once a year for as long as you take this drug. Make sure to ask your physician what the unique benefits and risks of metformin will be for you. If you doctor prescribes Glucophage without a careful review of your health status and without involving you in the decision, find another doctor.

Answer 2

Hello, I have type 2 diabetes, have done since 1982, i take 4x500mg daily as well as 4 Insulin Injections, i have had no side effects.