Biguanides belong to a group of oral medications known as antidiabetic agents, used to treat cases of type 2 diabetes that cannot be controlled solely by exercise and diet. They lower glucose (blood sugar) levels by preventing the liver from producing too much glucose and reduce the amount of glucose from dietary sources. They also increase the sensitivity of muscle tissue to insulin, a hormone made in the pancreas that carries glucose from the bloodstream into the cells. Biguanides also slow the absorption of glucose from food digested in the small intestine.

In type 2 diabetes, glucose builds up in the bloodstream (hyperglycemia) because the cells are resistant to absorbing it. This insulin resistance triggers many health problems that, among other things, increase the risk for heart attack and stroke. These conditions include:

• Obesity
• High blood pressure
• High levels of triglycerides and LDL “bad” cholesterol
• Low levels of HDL “good” cholesterol
• High levels of insulin in the blood (hyperinsulinemia)

Biguanides lower glucose by regulating the amount of it in the bloodstream. They also help insulin to move glucose into the cells.

Glucose is a major source of energy for the cells in the body. People get glucose from the foods they eat and from their liver, which produces glucose as a source of energy between meals, particularly at night. However, the liver often begins to overproduce glucose in patients with type 2 diabetes. This can contribute to hyperglycemia.

Glucose control is the main advantage of using biguanides but not the only benefit. Biguanides have also been shown to decrease levels of blood fats (lipids) such as triglycerides and LDL cholesterol. Unlike many antidiabetic agents, biguanides do not cause patients to gain weight. In fact, many patients find that biguanides help them lose weight.

These factors may help reduce the risk of developing diseases of the large blood vessels such as atherosclerosis (narrowing and hardening of the arteries) and heart conditions.

Another advantage of biguanides is that, unlike many other antidiabetic agents, they do not trigger hypoglycemia. In contrast, many other antidiabetic agents increase insulin production, which boosts the risk of low glucose.

In addition, biguanides can be a good alternative for patients whose sulfa allergies prevent treatment with certain other antidiabetic agents.

Biguanides were introduced into the United States in 1977, but the Food and Drug Administration (FDA) restricted their use after complications from phenformin were reported. However, the FDA reinstated biguanides in 1994 after they had earned long-term track records of safety in Europe (30 years) and Canada (20 years). In 2005, researchers reviewing 29 clinical trials involving more than 5,000 patients compared the biguanide metformin to other treatments for type 2 diabetes. This meta-analysis found that metformin especially benefited obese patients in controlling glucose, weight, blood pressure and blood fats such as cholesterol.

Recent research suggests that patients' response to metformin may be gauged early. Those who have significant improvements in glucose control or weight loss within the first year of therapy may not need a different or additional drug for years to come.

The landmark Diabetes Prevention Program (DPP) found that people with prediabetes who took metformin reduced their risk of becoming diabetic, though not as much as the group that relied on exercise and diet. A recent follow-up to the DPP found antidepressants to be a risk factor for developing diabetes, but no increased risk was noted in those who also took metformin. Further study would be needed to explain why use of metformin may reduce risk of diabetes in people who use antidepressants.

Researchers are investigating metformin as a treatment for polycystic ovarian syndrome (PCOS), an endocrine disorder that girls and women with prediabetes and type 2 diabetes have an increased risk of developing. Other treatments for PCOS include ovulation (fertility) drugs, which are usually the first line of treatment. The FDA has not specifically approved metformin to treat PCOS, prediabetes or insulin resistance, but some physicians prescribe it "off label" for these purposes. Researchers are also studying metformin as a means of preventing weight gain in children taking certain antipsychotic medications.

Biguanides generally are taken two to three times daily with meals. A physician can advise individual patients about the best times for them to take these drugs. The extended-release formula of these drugs is taken once daily, usually with dinner.

Patients who forget to take their dose of biguanides may be advised by their physician or pharmacist to make up the dose only if it is within two hours of their regularly scheduled time. Patients should ask in advance what to do if more than two hours have elapsed, or contact their physician if they have not asked earlier. It is important not to take two doses in close proximity.

In some cases, the glucose-reducing effects of biguanides can be combined with the insulin-enhancing effects of another antidiabetic agent, such as a sulfonylurea, thiazolidinedione or DPP-4 inhibitor. Biguanides also are sometimes prescribed in tandem with insulin injections.