Metformin is a drug commonly used in the treatment of Type 2 diabetes. It is sold as a generic and under several brand names, including Glucophage, Glumetza, Riomet, and Fortamet. Both the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) recommend metformin as a cornerstone of therapy for Type 2 diabetes when exercise and dietary changes aren’t enough to keep blood glucose levels in target range. The low cost of the generic forms along with a long history of use make it a good choice for many individuals with Type 2 diabetes.
Although metformin has helped many people lower their blood glucose levels, it does have some potential side effects that are worth knowing about. Understanding the risks and benefits of metformin is key to using it successfully. Take this quiz to test your knowledge of this popular diabetes medicine. (You can find the answers later in the article.)
1. How does metformin work to lower blood glucose levels?
A. It stimulates the pancreas to make more insulin.
B. It decreases the amount of glucose produced by the liver and makes it easier for cells to accept glucose from the bloodstream.
C. It slows the digestive system’s breakdown of carbohydrates into glucose, allowing more time for insulin to work.
D. It suppresses appetite, slows stomach emptying, and inhibits the release of glucagon (a hormone that raises blood glucose levels).
2. In addition to lowering blood glucose, metformin sometimes causes moderate weight loss.
3. In research studies, metformin use was associated with which of the following benefits in people with Type 2 diabetes?
A. Reduced risk of morning high blood glucose.
B. Reduced neuropathy (nerve damage).
C. Reduced retinopathy (damage to the retina, a membrane in the eye).
D. Reduced nephropathy (kidney disease).
4. Which of the following are potential side effects of metformin?
B. Gastrointestinal upset.
C. Vitamin B12 deficiency.
D. Heart attack.
5. Metformin should be used with caution by people with nephropathy (kidney disease), severe liver disease, or decreased kidney function.
6. Under which of the following circumstances should you remind your doctor that you are taking metformin?
A. Before an x-ray test that uses an injected dye.
B. Before surgery.
C. Before starting any new drugs, for your diabetes or for any other condition.
D. Before beginning an exercise regimen.
1. B and C. Metformin works by activating an enzyme called AMP-activated protein kinase (AMPK), that in turn signals the liver to produce less glucose and encourages cells to store glucose from the bloodstream (thus lowering blood glucose levels). AMPK also affects the body’s metabolism by inhibiting the production of cholesterol and fatty acids and lowering insulin resistance. Additionally, metformin may decrease the absorption of glucose by the gastrointestinal tract, allowing more time for insulin to work and reducing postmeal spikes in blood glucose level.
2. TRUE. The change may not be dramatic, but generally, people who take metformin lose some weight within a few months of starting treatment. Metformin is different in this regard from other diabetes medicines, such as sulfonylureas (glimepiride, glyburide, glipizide), thiazolidinediones (Actos and Avandia), or insulin, which often lead to weight gain. In all of these cases, however, careful attention to food choices and portion sizes and getting regular physical activity can minimize or prevent weight gain. In the case of insulin, tailoring dose sizes to the body’s needs will also prevent weight gain as a drug side effect.
3. A, B, C, and D. Metformin reduces the overproduction of glucose by the liver, which is what frequently causes high morning blood glucose. In fact, metformin is often first prescribed because of high morning blood glucose, and research bears out its effectiveness at alleviating this common problem. Long-term research studies (those lasting five years or longer) have also shown metformin to reduce damage to the small blood vessels, a common consequence of chronic high blood glucose. Conditions that can result from this damage include neuropathy, retinopathy, and nephropathy.
4. B and C. The most common side effects of metformin are related to the intestines. Diarrhea is the most common, but some people report problems with the upper digestive tract, such as nausea or heartburn. Metformin is usually started at a low dose to reduce these side effects, then gradually increased as the body adjusts to the drug. Gastrointestinal side effects can also be reduced by taking metformin with a meal. Full benefits of metformin (including lower blood glucose) are often not seen until the dose is adjusted upward. This usually takes a couple of weeks.
Reduced vitamin B12 absorption is another possible side effect of metformin, leading to a deficiency in 10% to 30% of the people who take it. Vitamin B12 deficiency can cause anemia and nerve damage. If you take metformin, ask your doctor about having your B12 level measured and about whether you should take B12 supplements.
Use of metformin is not associated with insomnia. In addition, a long-term study of people with Type 2 diabetes treated soon after diagnosis with metformin showed a lowered risk of death, heart attack, and vascular problems; whether these benefits extend to everyone who takes it is not known.
5. TRUE. The kidneys are responsible for removing metformin from the body. In people with kidney damage, metformin can build up in the blood, leading to a rare but serious condition called lactic acidosis. However, research has shown metformin to have a protective effect on the kidneys if started before damage has been done; it does not cause kidney damage in healthy kidneys. Severe liver disease also increases a person’s risk of developing lactic acidosis. Some doctors prescribe metformin for people with mild nonalcoholic fatty liver disease. Your doctor will closely monitor your liver with blood tests if you are taking metformin and have a history of liver disease.
6. A, B, and C. Dyes that are used in some x-ray tests can, in rare instances, cause temporary kidney shutdown, possibly leading to lactic acidosis. Your doctor may advise you to stop taking metformin for two days before and two days after such an x-ray to avoid problems. Major surgery can lead to reduced fluids in the blood and sometimes reduced kidney function, raising the risk of lactic acidosis. Metformin may need to be stopped before surgery.
Like any drug, metformin can interact with certain other drugs. Before you start any new drugs, therefore, ask your doctor about potential interactions and what the symptoms of such interactions might be. Your pharmacist is another good source of information on drug interactions and side effects.
It’s always a good idea to check in with your doctor before starting an exercise program or intensifying your workouts. But taking metformin should not hinder or interfere with your ability to exercise.