Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polyendocrine metabolic ovarian syndrome, and is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotic medication. It has been shown to inhibit inflammation, and is not associated with weight gain. Metformin is taken by mouth. Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. It has a small risk of causing low blood sugar. High blood lactic acid level (acidosis) is a concern if the medication is used in overly large doses or prescribed to people with severe kidney problems. Metformin is a biguanide anti-hyperglycemic agent. It works by decreasing glucose production in the liver, increasing the insulin sensitivity of body tissues, and increasing GDF15 secretion, which reduces appetite and caloric intake. Metformin was first described in the scientific literature in 1922 by Emil Werner and James Bell. French physician Jean Sterne began the study in humans in the 1950s. It was introduced as a medication in France in 1957. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the second most commonly prescribed medication in the United States, with more than 85 million prescriptions. In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023.
Medical uses Metformin is used to lower blood glucose in those with type 2 diabetes. It has also been used to help with metabolic abnormalities in polyendocrine metabolic ovarian syndrome (PMOS), and as a second-line agent for infertility in those with PMOS.
Type 2 diabetes The American Diabetes Association and the American College of Physicians both recommend metformin as a first-line agent to treat type 2 diabetes. It is as effective as repaglinide and more effective than all other oral drugs for type 2 diabetes.
Efficacy Some evidence shows 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 low density lipoprotein and triglyceride levels. In individuals with prediabetes, a 2019 systematic review comparing the effects of metformin with other interventions in the reduction of risk of developing type 2 diabetes found moderate-quality evidence that metformin reduced the risk of developing type 2 diabetes when compared to diet and exercise or a placebo. However, when comparing metformin to intensive diet or exercise, moderate-quality evidence was found that metformin did not reduce risk of developing type 2 diabetes and very low-quality evidence was found that adding metformin to intensive diet or exercise did not show any advantage or disadvantage in reducing risk of type 2 diabetes when compared to intensive exercise and diet alone. The same review also found one suitable trial comparing the effects of metformin and sulfonylurea in reducing the risk of developing type 2 diabetes in prediabetic individuals; however, this trial did not report any patient-relevant outcomes.
Polyendocrine metabolic ovarian syndrome In those with polyendocrine metabolic ovarian syndrome (PMOS), tentative evidence shows that metformin use increases the rate of live births. This includes those who have not been able to get pregnant with clomiphene. Metformin does not appear to change the risk of miscarriage. A number of other benefits have also been found both during pregnancy and in nonpregnant people with PMOS. In an updated Cochrane review on metformin versus placebo/no treatment before or during IVF/ICSI in women with PMOS, no conclusive evidence of improved live birth rates was found. In long GnRH-agonist protocols there was uncertainty in the evidence of improved live birth rates but there could be increases in clinical pregnancy rate. In short GnRH-antagonist protocols metformin may reduce live birth rates with uncertainty on its effect on clinical pregnancy rate. Metformin may result in a reduction of OHSS but could come with a greater frequency of side effects. There was uncertainty as to metformin's impact on miscarriage. The evidence does not support general use during pregnancy for improving maternal and infant outcomes in obese women. The United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that people with PMOS and a body mass index above 25 be given metformin for anovulation and infertility when other therapies fail to produce results. UK and international clinical practice guidelines do not recommend metformin as a first-line treatment or do not recommend it at all, except for people with glucose intolerance. The guidelines suggest clomiphene as the first medication option and emphasize lifestyle modification independently from medical treatment. Metformin treatment decreases the risk of developing type 2 diabetes in people with PMOS who exhibited impaired glucose tolerance at baseline. In Poland, metformin is listed as an approved and reimbursed treatment for PMOS.
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