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    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. 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. 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. 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. 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. 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. May be used in combination with a sulfonylurea, repaglinide, or thiazolidinedione antidiabetic agent for the management of type 2 diabetes mellitus in patients who do not achieve adequate glycemic control on monotherapy with metformin or any of these drugs. Commercially available in fixed combination with pioglitazone (as immediate- or extended-release tablets) for use as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who have inadequate glycemic control with pioglitazone or metformin monotherapy or in those who are already receiving pioglitazone and metformin concurrently as separate components. Commercially available in fixed combination with repaglinide for use as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who are already receiving repaglinide and metformin concurrently as separate components or in those who have inadequate glycemic control with repaglinide or metformin monotherapy. Potential advantages of metformin compared with sulfonylureas or insulin include minimal risk of hypoglycemia, more favorable effects on serum lipids, reduction of hyperinsulinemia, and weight loss or lack of weight gain. Scientific Advisory Panel of the Executive Committee, American Diabetes Association. Increase daily dosage in increments of one tablet (using the tablet strength at which therapy was initiated) at 2-week intervals until adequate glycemic control is achieved or maximum daily dosage of 2 g of metformin hydrochloride and 10 mg of glipizide is reached. Patients with inadequate glycemic control on either a sulfonylurea or metformin alone: Initially, 500 mg of metformin hydrochloride and 2.5 or 5 mg of glipizide twice daily with the morning and evening meals. Titrate daily dosage in increments not exceeding 500 mg of metformin hydrochloride and 5 mg of glipizide until adequate glycemic control achieved or maximum daily dosage of 2 g of metformin hydrochloride and 20 mg of glipizide is reached.

    Metformin administration

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