![]() ![]() There was uncertainty as to metformin's impact on miscarriage. Metformin may result in a reduction of OHSS but could come with a greater frequency of side effects. In short GnRH-antagonist protocols metformin may reduce live birth rates with uncertainty on its effect on clinical pregnancy rate. 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 an updated Cochrane (2020) review on metformin versus placebo/no treatment before or during IVF/ICSI in women with PCOS no conclusive evidence of improved live birth rates was found. A number of other benefits have also been found both during pregnancy and in nonpregnant women with PCOS. Metformin does not appear to change the risk of miscarriage. This includes in those who have not been able to get pregnant with clomiphene. In those with polycystic ovarian syndrome (PCOS), tentative evidence shows that metformin use increases the rate of live births. The same review also found one suitable trial comparing the effects of metformin and sulfonylurea in reducing risk of developing type 2 diabetes in prediabetic individuals, however this trial did not report any patient relevant outcomes. 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. 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. Metformin modestly reduces low density lipoprotein and triglyceride levels. 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. ![]() Some evidence shows that metformin is associated with weight loss in obesity in the absence of diabetes. The use of metformin reduces body weight in people with type 2 diabetes in contrast to sulfonylureas, which are associated with weight gain. A 2020 Cochrane systematic review did not find enough evidence of reduction of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke when comparing metformin monotherapy to other glucose-lowering drugs, behaviour change interventions, placebo or no intervention. 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, describe evidence for the cardiovascular benefits of metformin as equivocal. It is as effective as repaglinide and more effective than all other oral drugs for 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 also used as a second-line agent for infertility in those with polycystic ovary syndrome. Metformin is used to lower the blood glucose in those with type 2 diabetes. In 2020, it was the third most commonly prescribed medication in the United States, with more than 92 million prescriptions. ![]() Metformin is on the World Health Organization's List of Essential Medicines, and is the most widely used medication for diabetes taken by mouth. It was introduced as a medication in France in 1957 and the United States in 1995. French physician Jean Sterne began the study in humans in the 1950s. Metformin was first described in scientific literature in 1922 by Emil Werner and James Bell. 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 is a biguanide anti- hyperglycemic agent. High blood lactic acid level ( acidosis) is a concern if the medication is used in overly large doses or prescribed in people with severe kidney problems. It has a small risk of causing low blood sugar. Common adverse effects include diarrhea, nausea, and abdominal pain. Metformin is not associated with weight gain and is taken by mouth. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. ![]() It is also used in the treatment of polycystic ovary syndrome. 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. ![]()
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