«Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome (PCOS). Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes. It is not associated with weight gain. It is taken by mouth.
Metformin is generally well tolerated. Common side effects include diarrhea, nausea and abdominal pain. It has a low risk of causing low blood sugar.High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses. It should not be used in those with significant liver disease or kidney problems. While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes. Metformin is in the biguanide class. It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.
Metformin was discovered in 1922. French physician Jean Sterne began study in humans in the 1950s. It was introduced as a medication in France in 1957 and the United States in 1995. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Metformin is believed to be the most widely used medication for diabetes which is taken by mouth. It is available as a generic medication. The wholesale price in the developed world was between US$0.21 and US$5.55 per month as of 2014. In the United States, it costs US$5 to US$25 per month. In 2016 it was the 4th most prescribed medication in the United States with more than 81 million prescriptions.
Metformin is primarily used for type 2 diabetes, but is also used in polycystic ovary syndrome. Outcomes appear to be improved even in those with some degree of kidney disease, heart failure, or liver problems.
The American Diabetes Association and the American College of Physicians each recommend metformin as a first-line agent to treat type 2 diabetes.
The UK Prospective Diabetes Study, a large clinical trial performed in 1980-90s, provided evidence that metformin reduced the rate of adverse cardiovascular outcomes in overweight patients with type 2 diabetes relative to other antihyperglycemic agents. However, accumulated evidence from other and more recent trials reduced confidence in the efficacy of metformin for cardiovascular disease prevention.
Treatment guidelines for major professional associations including the European Association for the Study of Diabetes, the European Society for Cardiology and the American Diabetes Association, now describe evidence for the cardiovascular benefits of metformin as equivocal.
In 2017, the American College of Physicians's guidelines were updated to recognize metformin as the first-line treatment for type-2 diabetes. These guidelines supersede earlier reviews. For example, a 2014 review found tentative evidence that people treated with sulfonylureas had a higher risk of severe low blood sugar events (RR 5.64), though their risk of non-fatal cardiovascular events was lower than the risk of those treated with metformin (RR 0.67). There was not enough data available at that time to determine the relative risk of death or of death from heart disease.
Metformin has little or no effect on body weight in type 2 diabetes compared with placebo, in contrast to sulfonylureas which are associated with weight gain. There is some evidence that metformin is associated with weight loss in obesity in the absence of diabetes. Metformin has a lower risk of hypoglycemia than the sulfonylureas, although hypoglycemia has uncommonly occurred during intense exercise, calorie deficit, or when used with other agents to lower blood glucose. Metformin modestly reduces LDL and triglyceride levels.
Metformin treatment of people at a prediabetes stage of risk for type 2 diabetes may decrease their chances of developing the disease, although intensive physical exercise and dieting work significantly better for this purpose. In a large U.S. study known as the Diabetes Prevention Program, participants were divided into groups and given either placebo, metformin, or lifestyle intervention and followed for an average of three years.
The intensive program of lifestyle modifications included a 16-lesson training on dieting and exercise followed by monthly individualized sessions with the goals of decreasing weight by 7% and engaging in physical activity for at least 150 minutes per week.
The incidence of diabetes was 58% lower in the lifestyle group and 31% lower in individuals given metformin. Among younger people with a higher body mass index, lifestyle modification was no more effective than metformin, and for older individuals with a lower body mass index, metformin was no better than placebo in preventing diabetes. After ten years, the incidence of diabetes was 34% lower in the group of participants given diet and exercise and 18% lower in those given metformin. It is unclear whether metformin slowed down the progression of prediabetes to diabetes (true preventative effect), or the decrease of diabetes in the treated population was simply due to its glucose-lowering action (treatment effect).» (wikipedia)
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