Biguanides for Type 2 Diabetes

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Biguanides for Type 2 Diabetes


Generic NameBrand Name
rosiglitazone and metforminAvandamet

In some cases, a doctor may recommend metformin for people who have prediabetes.

How It Works

The action of biguanides in treating type 2 diabetes is not completely understood. They lower blood sugar by:

  • Decreasing the amount of sugar produced by the liver. This is the primary action of these medicines.
  • Increasing the amount of sugar absorbed by muscle cells and decreasing the body's insulin resistance.

Metformin does not cause the pancreas to produce more insulin. And when taken alone, it should not cause low blood sugar (hypoglycemia) or weight gain. Some people taking metformin may lose weight.

Metformin may lower the amount of fat (triglycerides) in the bloodstream, which may reduce the risk of heart disease. It also has been shown to reduce certain abnormal clotting factors and markers of inflammation that can lead to hardening of the arteries.

Why It Is Used

These medicines can be used to treat people who have type 2 diabetes and who have not been able to keep their blood sugar levels within the target range by eating a balanced diet, losing weight, and exercising regularly. Metformin may be used alone or along with a sulfonylurea or thiazolidinedione medicine.

Metformin can also be used to treat people who have type 2 diabetes and who need to take insulin. A study showed that adding metformin to insulin therapy improved blood sugar levels better than increasing the dose of insulin and did not cause weight gain.1 Metformin may also be used with liraglutide, pioglitazone, and sitagliptin.

People who have very low insulin levels, have other severe medical conditions (such as kidney, liver, heart, or lung disease), or are having major surgery should not take biguanides.

Metformin is the oral medicine of choice for treating type 2 diabetes in children and adolescents.4

In some cases, a doctor may recommend metformin for people who have prediabetes.

How Well It Works

Studies have shown that metformin:

  • Was as effective as sulfonylurea medicines in reducing blood sugar levels in people with type 2 diabetes.2
  • Reduced the risk of complications from diabetes in people who were overweight. People who were overweight did not gain weight while taking metformin.3

People who have just been diagnosed with type 2 diabetes may be able to keep their blood sugar levels within a target range by taking metformin. But even though metformin controls blood sugar levels for a longer period of time than sulfonylurea medicines, over time it may become less effective.

In studies, a combination of metformin and glyburide caused a greater decrease in blood sugar levels than glyburide or metformin alone. Sometimes a combination of metformin and a sulfonylurea effectively controls blood sugar when a sulfonylurea medicine alone has not been effective.

People usually do not gain weight and may even lose a small amount of weight when taking metformin. (People taking sulfonylurea medicines or insulin may gain weight.)

Metformin is as effective in treating children with type 2 diabetes as it is in treating adults.4

Side Effects

The most common side effects of metformin are:

  • Temporary nausea.
  • Loss of appetite.
  • Diarrhea.
  • Increased abdominal gas.
  • A metallic taste.

These side effects occur in 5% to 20% of people taking metformin.2 Side effects usually decrease over time. When a person begins taking metformin, the dosage usually is increased gradually to prevent side effects. You may also reduce nausea by taking the medicine with food.

Blood levels of vitamin B12 can decrease in some people who take metformin. But this usually does not cause health problems.2

A rare side effect of metformin is a condition called lactic acidosis. Lactic acidosis occurs when muscles release lactic acid during exercise. If the liver is not able to convert the lactic acid into sugar, the acid builds up in the blood. If lactic acidosis is not treated quickly, it can lead to coma and death.

  • Lactic acidosis may occur in people who have kidney or liver failure, have low levels of oxygen in their blood (hypoxia), abuse alcohol, or are dehydrated. It can also result if metformin is taken when a person has surgery or X-ray studies that use a dye. Be sure all your doctors know that you are taking this medicine if you need a test that involves the use of a dye or if you are having surgery. You will have to stop taking metformin for up to 48 hours before and after the test or surgery.
  • Metformin should not be used to treat diabetes in people who have decreased kidney or liver function. A blood test to measure kidney and liver function should be done before starting this medicine.

Metformin may decrease menstrual irregularities in women with polycystic ovary syndrome. This may increase the risk for unplanned pregnancy.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Biguanides do not cause low blood sugar (hypoglycemia) or weight gain, which are common side effects of the sulfonylurea medicines.

Metformin (Glucophage) has to be taken 2 to 3 times a day, but the extended-release form (Glucophage XR) can be taken just once a day. Both are available in generic form. Some people may have fewer gastrointestinal side effects with Glucophage XR than with Glucophage.

Although metformin may be safe to take during pregnancy, the U.S. Food and Drug Administration (FDA) has not approved it for that use. Talk with your doctor immediately if you become pregnant while taking metformin.

The effect of metformin may be increased if you also take cimetidine (Tagamet). Talk with your doctor if you are taking Tagamet.

Health Canada and the U.S. Food and Drug Administration (FDA) have announced a possible safety issue with the drug rosiglitazone (Avandia). A new study shows that people who take Avandia may raise their chance of having a heart attack. They may also raise their chance of death from heart disease.

Manufacturers of rosiglitazone (Avandia), pioglitazone (Actos), rosiglitazone and glimepiride (Avandaryl) and rosiglitazone and metformin (Avandamet) have added a warning that these drugs may cause heart failure or make heart failure worse in certain people.

Metformin is avoided in people with unstable heart failure.

If you take any of these medicines, do not stop taking them. Call your doctor to talk about which medicine is best for you.

Metformin usually keeps blood sugar levels within a target range without increasing the likelihood that you will gain weight. If after 3 to 6 months of treatment with metformin blood sugar levels are not consistently within your target range, a sulfonylurea or insulin is usually added.

Metformin should be stopped during an illness that causes vomiting or diarrhea or any condition that causes dehydration. Check with your doctor.


Few studies have been done on the use of oral medicines for type 2 diabetes in children. And these medicines have not been approved by the Therapeutic Products Directorate (TPD) for use in children. But because these oral medicines are safe for adults, many doctors use them to treat children who have type 2 diabetes.

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.



  1. American Diabetes Association (2009). Medical management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care, 32: 193–203.
  2. Lebowitz HE (2005). Management of hyperglycemia with oral antihyperglycemic agents in type 2 diabetes. In CR Kahn et al., eds., Joslin's Diabetes Mellitus, 14th ed., pp. 687–710. Philadelphia: Lippincott Williams and Wilkins.
  3. Riddle MC, Genuth S (2010). Type 2 diabetes mellitus. In EG Nabel, ed., ACP Medicine, section 9, chap. 2. Hamilton, ON: BC Decker.
  4. Jones KL, et al. (2002). Effect of metformin in pediatric patients with type 2 diabetes. Diabetes Care, 25(1): 89–94.


By Healthwise Staff
Primary Medical Reviewer E. Gregory Thompson, MD - Internal Medicine
Primary Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Specialist Medical Reviewer Matthew I. Kim, MD - Endocrinology
Last Revised August 4, 2010

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