A popular oral drug for treating Type 2 diabetes. Metformin (brand name Glucophage, Glucophage XR, Glumetza, Riomet) is a member of a class of drugs called biguanides that helps lower blood glucose levels by improving the way the body handles insulin — namely, by preventing the liver from making excess glucose and by making muscle and fat cells more sensitive to available insulin.

Metformin not only lowers blood glucose levels, which in the long term reduces the risk of diabetic complications, but it also lowers blood cholesterol and triglyceride levels and does not cause weight gain the way insulin and some other oral blood-glucose-lowering drugs do. Overweight, high cholesterol, and high triglyceride levels all increase the risk of developing heart disease, the leading cause of death in people with Type 2 diabetes. Another advantage of metformin is that it does not cause hypoglycemia (low blood glucose) when it is the only diabetes medicine taken. Metformin is typically taken two to three times a day, with meals. The extended-release formula (Glucophage XR) is taken once a day, with the evening meal.

The most common side effects of metformin are nausea and diarrhea, which usually go away over time. A more serious side effect is a rare but potentially fatal condition called lactic acidosis, in which dangerously high levels of lactic acid build up in the bloodstream. Lactic acidosis is most likely to occur in people with kidney disease, liver disease, or congestive heart failure, or in those who drink alcohol regularly. (If you have more than four alcoholic drinks a week, metformin may not be the best medicine for you.) Unfortunately, many doctors ignore these contraindications (conditions that make a particular treatment inadvisable) and prescribe metformin to people at increased risk for lactic acidosis. The early symptoms of lactic acidosis include unusual fatigue, nausea, vomiting, loss of appetite, muscle pain, and breathing difficulties. If you experience any of these symptoms while taking metformin, be sure to call your doctor at once. Metformin therapy should be stopped at least 48 hours before surgery and resumed only when you are eating normally again.

Metformin changed the landscape of diabetes treatment when the U.S. Food and Drug Administration (FDA) approved it for marketing in 1994. At the time, there were only two other types of medicine available in the United States for treating Type 2 diabetes: sulfonlyureas, a class of oral drugs that lowers blood glucose by stimulating the pancreas to secrete more insulin. Since metformin was approved in the United States, a number of other classes of diabetes medicines have come to the marketplace that lower blood glucose levels through a variety of mechanisms. These include alpha-glucosidase inhibitors, which slow the absorption of carbohydrate in the small intestine, causing a slower rise in blood glucose level after meals; thiazolidinediones, which enhance insulin sensitivity; meglitinides, which stimulate rapid insulin secretion from the pancreas after meals by a different mechanism than that of older sulfonylureas; GLP-1 agonists, which delay stomach emptying and stimulate insulin secretion; DPP-4 inhibitors, which enhance insulin secretion and delay stomach emptying; amylin analogs, which slow stomach emptying, suppress glucagon, and suppress appetite; GLP-1 receptor agonists, which increase satiety (feelings of fullness), slow stomach emptying, increase insulin release, and decrease glucagon release; and SGLT2 inhibitors, which block the reabsorption of glucose by the kidneys. Because these medicines have different mechanisms of action, doctors often combine different classes of medicines for a more powerful blood-glucose-lowering effect.

Since metformin is often prescribed together with other diabetes drugs, some manufacturers have started combining two drugs in a single pill for more convenient therapy. These include Kazano, Invokamet, Invokamet XR, Xigduo XR, Synjardy, Synjardy XR, Metaglip, Glucovance, Jentadueto, Jentadueto XR, PrandiMet, Avandamet, Kombiglyze XR, Janumet, and Janumet XR. Anyone taking one of these pills should be alert to the symptoms of lactic acidosis.

Want to learn more about this popular diabetes drug? Read “Diabetes Medicine: Metformin,” “Metformin: The Unauthorized Biography,” and “Metformin Smelling Fishy? What You Can Do,” then take our quiz, “How Much Do You Know About Metformin?”

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