Metformin for Patients with Type 2 Diabetes Mellitus

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The summary below is from the full report titled "Metformin: An Update." It is in the 2 July 2002 issue of Annals of Internal Medicine (volume 137, pages 25-33). The authors are D Kirpichnikov, SI McFarlane, and JR Sowers.

What is the problem and what is known about it so far?

Diabetes mellitus is a disease characterized by high levels of sugar (glucose) in the blood. Insulin (a chemical produced by the pancreas) helps regulate the level of glucose in the blood by facilitating its passage into the cells of the body, where it is used as a nutrient. When glucose enters cells, it is effectively removed from the blood and its concentration in the bloodstream decreases. Two types of diabetes mellitus are recognized. Type 1 (juvenile) diabetes is caused by a failure of the pancreas to produce insulin, while type 2 (adult-onset or non-insulin-dependent) diabetes results from resistance of cells to respond to insulin's usual effects. Although extra insulin output initially overcomes cells' resistance, the pancreas eventually fails to produce enough to do the job effectively. Many experts believe that type 2 diabetes is one component of a "metabolic syndrome" that includes obesity, cholesterol disorders, hypertension, and blood clotting abnormalities.

Why did the authors do this update?

To update doctors on the effectiveness of metformin, a drug used to treat high blood sugar and other components of the metabolic syndrome.

How did the authors do this update?

They looked at numerous studies that followed patients treated with metformin alone or in combination with other drugs and articles dealing with the metabolic syndrome.

What did the authors find?

Metformin is effective in decreasing cells' resistance to insulin. By itself, metformin is as effective as another group of drugs used to lower blood sugar (sulfonylureas), and when used along with diet modification, it substantially reduces the fasting blood sugar level. When taken in combination with other agents, it is frequently more effective than any single drug used to lower blood glucose levels.

The exact way metformin works is unclear, but the drug also appears to improve or correct other conditions associated with the metabolic syndrome, such as high fat levels in the blood, the way calcium enters cells, blood clotting abnormalities, and obesity. When compared with conventional diabetes therapy, metformin significantly reduces the risk for heart attack, diabetes-related death, and overall death. Metformin is especially well suited for treatment of obese diabetic persons with normal kidney function. The drug may not be appropriate for thin elderly patients.

Dose of the drug should be increased gradually to allow the body to adjust to its effects. Common side effects are nausea and diarrhea, which usually disappear within 2 weeks. Metformin may be associated with a life-threatening buildup of lactic acid in the blood (lactic acidosis) and is not appropriate for people with liver failure, a history of alcohol abuse, or active infections.

What are the implications of this update?

Physicians should consider prescribing metformin, alone or in combination with other therapies, for patients with type 2 diabetes mellitus, particularly those who are obese and have normal kidney function.